贯叶连翘中二蒽酮类化合物免疫活性研究及其白蛋白-IgG抗体偶联物的研制
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摘要
贯叶连翘（HypericumperforatumLinn.）提取物包含很多类复杂的成分，每一类成分都有其不同的药理作用。二蒽酮类化合物就是其中的一类，主要包括金丝桃素、伪金丝桃素、原金丝桃素、原伪金丝桃素、环金丝桃素等，二蒽酮类化合物具有很多药理作用如抗炎、抗抑郁、抗肿瘤及抗病毒作用，目前其研究存在几个问题，1、抗病毒机理不明确。2、药物的生物利用度低。3、对机体作用部位不明。针对抗病毒机理问题，本文从免疫学角度研究了二蒽酮类化合物对免疫器官及机体相关酶和细胞因子的作用，并探讨了对机体免疫相关网络的影响，阐述了其可能的抗病毒机理之一其就是增强机体的免疫力。针对其生物利用度的问题，本文将其用生物可降解材料白蛋白包裹，制成药物白蛋白包合物，提高了药物的生物利用度，提高了其有效含量。针对其作用部位不明确的问题，本文将二蒽酮类化合物白蛋白包合物与IgG抗体偶联，并进行初步检测，这为构建药物定向给药系统提供理论依据。主要研究内容如下：
1.二蒽酮类对小鼠免疫功能和抗氧化能力的影响。通过测定小鼠的脾脏指数和胸腺指数，与自由基产生和清除相关的6种酶（T-AOC、T-SOD、MPO、XOD、GSH-PX、POD）活性，及体内MDA、H_2O_2和NO水平，并对免疫器官作组织病理学观察，得出以下结论：二蒽酮类能够显著提高小鼠脾脏指数，极显著降低小鼠的MDA、NO和XOD水平（P<0.01），极显著提高小鼠的T-SOD，T-AOC，GSH-PX，POD水平（P<0.01），对H_2O_2的水平没有影响。表明二蒽酮类能通过提高脾脏指数，降低过氧化物产物MDA和NO水平，改变机体内对自由基产生和清除相关酶活性来影响体内自由基的产生和清除，使机体免疫器官免受损伤，以拮抗地塞米松所致的免疫抑制，增强机体的免疫功能。组织病理学观察结果表明二蒽酮类对免疫抑制小鼠的肝脏及脾脏具有一定的修复功能。胸腺也有一定恢复作用，但作用不明显。
2.二蒽酮类对小鼠T细胞表面膜分子及血清细胞因子的影响。采用ELISA法检测小鼠T细胞表面膜分子（CD3、CD4、CD8、CD4/CD8）及血清细胞因子（IL-4、IL-6、IL-10、IFN-γ、TNF-α）的水平，得出以下结论：二蒽酮类能够显著提高小鼠T淋巴细胞亚群CD3、CD4、CD8及CD4/CD8及细胞因子IFN-γ和TNF-α的水平，显著降低小鼠血清细胞因子IL-4、IL-6和IL-10的水平。表明二蒽酮类能够增加小鼠体内的成熟T细胞数量，促使T细胞释放各种细胞因子，以及调节机体内Th1细胞和Th2细胞的活性来上调机体免疫功能。
3.二蒽酮类对大鼠cAMP/cGMP信号通路的影响。采用ELISA法检测大鼠血清的cAMP和GMP水平，并计算二者比值，得出以下结论：二蒽酮类能够通过显著降低机体的cAMP水平，显著提高机体的cGMP的水平及cAMP/cGMP的比值来影响机体的cAMP/cGMP信号通路。表明二蒽酮类能够增强B淋巴细胞的分化与增殖，并促进其抗体生成，增强体液免疫的功能。
4.二蒽酮类对大鼠下丘脑-垂体-肾上腺轴的影响。采用ELISA法检测大鼠血清的ACTH和CORT水平，得出以下结论：二蒽酮类通过显著降低机体的ACTH和CORT的水平来影响大鼠下丘脑-垂体-肾上腺轴，表明二蒽酮类通过降低ACTH和CORT水平来促进T细胞转化，降低下丘脑-垂体-肾上腺轴功能亢进，使由于HPA轴功能亢进引起的下丘脑、垂体、肾上腺的功能异常，及免疫力低下效应减弱。
5.二蒽酮类对大鼠神经内分泌免疫的网络相关因子的影响。采用ELISA法检测大鼠神经内分泌免疫的网络相关因子IL-1、DA、NA和5-HT的水平，得出以下结论：二蒽酮类通过显著降低机体的IL-1、DA、NA和5-HT水平来影响神经内分泌免疫的网络。表明二蒽酮类可能影响血管加压素对肾上腺的作用，降低GC释放量使免疫过程的各个环节的抑制状态缓解，也可能影响垂体，通过ACTH水平降低来降低肾上腺皮质激素含量从而缓解抑制免疫状态，或者通过提高机体内DA的水平来抑制B细胞而增强T细胞和巨噬细胞的功能，从而使机体免疫功能恢复。
6.二蒽酮类白蛋白包合物的制备。采用去溶剂化-交联法制备二蒽酮类白蛋白包合物，并对其处方工艺进行优化，同时分析其形态，粒径及电位，测定其产率、包封率和载药量，并对其体外释放进行评价，得此包合物最佳制备工艺为：白蛋白加入量为1.5g，交联时间为24h，戊二醛用量为15μL，pH为9，乙醇滴加速度为1.0mL/min。其形态为球形，大小均一，平均粒径为122nm，电位值大于-50mv。产率、包封率和载药量分别为95.5%、71.43%和4.13%。此包合物在前4d的释放量占50%以上，4d到10d时，释放量约占总量的10%-15%，大约可持续4-5d，10d到25d时，药物浓度的变化不大。表明去溶剂化-交联法是一种适合二蒽酮类白蛋白包合物制备的方法，所制备的二蒽酮类白蛋白包合物形态规整、均一，稳定性好，具有高的产率、包封率及载药量，具有一定控缓释作用。
7.二蒽酮类白蛋白包合物与免疫球蛋白G抗体的偶联。采用戊二醛法制备二蒽酮类白蛋白包合物-免疫球蛋白G抗体偶联物，并对其偶联条件进行优化，用SDS-PAGE电泳检测。得二蒽酮类白蛋白包合物-免疫球蛋白G抗体偶联物最佳制备工艺：免疫球蛋白G抗体与包合物的质量比为1：1，戊二醛用量为总溶液体积的1/4，偶联时间为2h，温度为25℃，pH为中性。经SDS-PAGE电泳检测二蒽酮类白蛋白包合物-免疫球蛋白G抗体偶联物在210kDa附近有一条带。免疫球蛋白G抗体在150kDa附近有一条带，二蒽酮类白蛋白包合物在66kDa附近有一条带。这与理论上免疫球蛋白G抗体及二蒽酮类白蛋白包合物的分子量相符。表明去溶剂化-交联法是一种适合二蒽酮类白蛋白包合物制备的方法。
Hypericum extract contains numerous active compounds, each type of them have different pharmacological effects. Dianthrone is one of active compounds of Hypericum extract, including hypericin, pseudo hypericin, the original of hypericin, the original pseudo-hypericin, Central hypericin, etc. Dianthrone has many pharmacological effects such as anti-inflammatory, anti-depressants, anti-tumor and antiviral activity. There are several problems during the reasch,1. The anti-virus mechanism of Dianthrone is not clear.2. The low bioavailability of active ingredient.3. Site of action in the body is unknown. To the problems of the anti-virus mechanism, the roles of dianthrone on the immune organs, enzymes and cytokines were studied, the effects of dianthrone on the immune network were discussed, the conclusion of dianthrone antiviral mechanism was to be drawn, and which was to enhance the body's immunity. To increase the bioavailability, dianthrone was encapsulated in biodegradable materials bovine serum albumin (BSA) improving the bioavailability and effective content of dianthrone and also providing ideas for other similar active ingredients research. To clear the site of action in the body, dianthrone albumin clathrate and IgG antibodies were conjugated successfully, initial detection were conducted to provide a theoretical basis for targeted drug delivery systems. The research works were performd as follows.
1. Effects of dianthrone on immune function and antioxidant capability in mice. The thymus index, the spleen index, the activities of six enzymes(T-AOC、T-SOD、MPO、XOD、GSH-PX、POD), and the level of MDA, H2O2and NO were measured. Histopathological sections of immune organs have been observed. The following conclusions to be drawn: dianthrone had a functions to increase the spleen index, the level of T-SOD, T-AOC, GSH-PX and POD, decrease the level of MDA, NO and XOD, have no influence on the level of H2O2. The findings suggested that dianthrone could play an antioxidation activity by increasing spleen index, decreasing the level of MDA and NO, regulating activities of enzymes involved in production and elimination of free radicals in mice. The results of histopathological sections of immune organs showed that dianthrone has a repair function on the immune suppressed mice liver and spleen, and have a certain recovery on the thymus, but the effect is not obvious.
2. Effects of dianthrone on T cell surface film molecules and cytokines in serum in mice. The T cell surface film molecules(CD3、CD4、CD8、CD4/CD8) and cytokines (IL-4、IL-6、IL-10、IFN-γ、TNF-α) in serum were measured by ELISA method. The following conclusions to be drawn:dianthrone had functions to increase the T cell surface film molecules(CD3、 CD4、 CD8、 CD4/CD8) and cytokines (IFN-γand TNF-α) significantly, decrease level of IL-4、 IL-6、 IL-10. The findings suggested1dianthrone can increase the number of mature T cells, promote T cells to release cytokines, and regu the activity of Thl cells and Th2cells to increase the body's immune function.
3. Effects of dianthrone on cAMP/cGMP signaling pathway in rats. The level of cAMP and cGMP were measured by ELISA method, and the ratios of cAMP and cGMP were calculated. The following conclusions to be drawn: dianthrone had functions to increase the level of cAMP significantly, and decrease the level of cGMP and the ratios of cAMP and cGMP. The findings suggested that dianthrone can enhance the differentiation and proliferation of B lymphocytes, and promote the antibody generated to enhance the humoral immune function.
4. Effects of dianthrone on hypothalamic-pituitary-adrenal axis in rats. The level of ACTH and CORT were measured by ELISA method. The following conclusions to be drawn: dianthrone had functions to decrease the level of ACTH and CORT significantly. The findings suggested that dianthrone can decrease the level of ACTH and CORT to promote T cell transformation, reduce the hypothalamic-pituitary-adrenal axis hyperactivity to weak the dysfunction of hypothalamus, pituitary, adrenal and the effects of immunocompromised caused by HPA axis hyperactivity.
5. Effects of dianthrone on Neuroendocrine-immune network-related factor in rats.The level of IL-1, DA, NA and5-HT were measured by ELISA method, the following conclusions to be drawn: dianthrone had functions to decrease the level of IL-1, DA, NA and5-HT significantly. The findings suggested that dianthrone can affect the role of vasopressin on adrenal gland, reduce the GC release to alleviate the inhibition of the immune process. Or affect the level of ACTH in pituitary by reducing the level of Adrenal cortical hormone to alleviate the immunosuppressive. Or inhibition the function of B cells and enhanced the by increasing the level of DA torecover the immune function.
6. Preparation of dianthrone-loaded bovine serum albumin (BSA) clathrate. Used a desolvation-crosslinking method to prepare clathrate, and the prescription process was optimized. Its morphology, particle size distribution and potential distribution were estimated, the yield, encapsulation efficiency and drug loading were determined, the profile of in vitro drug release were assessed. The conditions for dianthrone-loaded bovine serum albumin clathrate preparation were optimized: the amount of albumin was1.5g, crosslinking time was24h, the amount of glutaraldehyde was15μL, pH was9, the dropping speed of ethanol was1.0mL/min. The surface morphology of the clathrate possessed smooth surfaces and spherical without any agglomeration. The mean size of the clathrate was122nm, and the zeta potential of the particles was greater than-50mV. The yield, encapsulation efficiency and drug-loading of the nanoparticles were95.5%,71.43%and4.13%, respectively. The drug release rate was greater than50%of entrapped in the BSA nanoparticles being released within4days, was10%-15%at4d to10d, and little change in drug concentration at10d to the25th day. The desolvation-crosslinking preparation method was a suitable preparation method for dianthrone albumin nanoparticles, the clathrate with a regular and uniform shape, high stability, yield, encapsulation efficiency and drug loading, and excellent controlled-release characteristics.
7. The conjunction of dianthrone albumin clathrate with IgG antibodies. Dianthrone albui clathrate and IgG antibodies were conjugated by glutaraldehyde method and optimized the conjunct conditions. The results were detected by SDS-PAGE electrophoresis. The conditions for dianthrone albumin clathrate-IgG antibody conjugates preparation were optimized: IgG antibodies and clathrate in the proportion of1:1, amount of Glutaraldehyde were1/4of the total volume of solution. Coupling time were2h, temperature were25℃and pH were neutral. Dianthrone albumin clathrate-IgG antibody conjugates were detected by SDS-PAGE electrophoresis. The results showed that dianthrone albumin clathrate-IgG antibody conjugates had a band near the210kDa, IgG antibody had a band near the150kDa, and dianthrone albumin clathrate had a band near the66kDa. The results were consistent with the theoretically molecular weight of IgG antibodies and dianthrone albumin clathrate. The glutaraldehyde method was a suitable preparation method for dianthrone albumin clathrate-IgG antibody conjugates.
1.二蒽酮类对小鼠免疫功能和抗氧化能力的影响。通过测定小鼠的脾脏指数和胸腺指数，与自由基产生和清除相关的6种酶（T-AOC、T-SOD、MPO、XOD、GSH-PX、POD）活性，及体内MDA、H_2O_2和NO水平，并对免疫器官作组织病理学观察，得出以下结论：二蒽酮类能够显著提高小鼠脾脏指数，极显著降低小鼠的MDA、NO和XOD水平（P<0.01），极显著提高小鼠的T-SOD，T-AOC，GSH-PX，POD水平（P<0.01），对H_2O_2的水平没有影响。表明二蒽酮类能通过提高脾脏指数，降低过氧化物产物MDA和NO水平，改变机体内对自由基产生和清除相关酶活性来影响体内自由基的产生和清除，使机体免疫器官免受损伤，以拮抗地塞米松所致的免疫抑制，增强机体的免疫功能。组织病理学观察结果表明二蒽酮类对免疫抑制小鼠的肝脏及脾脏具有一定的修复功能。胸腺也有一定恢复作用，但作用不明显。
2.二蒽酮类对小鼠T细胞表面膜分子及血清细胞因子的影响。采用ELISA法检测小鼠T细胞表面膜分子（CD3、CD4、CD8、CD4/CD8）及血清细胞因子（IL-4、IL-6、IL-10、IFN-γ、TNF-α）的水平，得出以下结论：二蒽酮类能够显著提高小鼠T淋巴细胞亚群CD3、CD4、CD8及CD4/CD8及细胞因子IFN-γ和TNF-α的水平，显著降低小鼠血清细胞因子IL-4、IL-6和IL-10的水平。表明二蒽酮类能够增加小鼠体内的成熟T细胞数量，促使T细胞释放各种细胞因子，以及调节机体内Th1细胞和Th2细胞的活性来上调机体免疫功能。
3.二蒽酮类对大鼠cAMP/cGMP信号通路的影响。采用ELISA法检测大鼠血清的cAMP和GMP水平，并计算二者比值，得出以下结论：二蒽酮类能够通过显著降低机体的cAMP水平，显著提高机体的cGMP的水平及cAMP/cGMP的比值来影响机体的cAMP/cGMP信号通路。表明二蒽酮类能够增强B淋巴细胞的分化与增殖，并促进其抗体生成，增强体液免疫的功能。
4.二蒽酮类对大鼠下丘脑-垂体-肾上腺轴的影响。采用ELISA法检测大鼠血清的ACTH和CORT水平，得出以下结论：二蒽酮类通过显著降低机体的ACTH和CORT的水平来影响大鼠下丘脑-垂体-肾上腺轴，表明二蒽酮类通过降低ACTH和CORT水平来促进T细胞转化，降低下丘脑-垂体-肾上腺轴功能亢进，使由于HPA轴功能亢进引起的下丘脑、垂体、肾上腺的功能异常，及免疫力低下效应减弱。
5.二蒽酮类对大鼠神经内分泌免疫的网络相关因子的影响。采用ELISA法检测大鼠神经内分泌免疫的网络相关因子IL-1、DA、NA和5-HT的水平，得出以下结论：二蒽酮类通过显著降低机体的IL-1、DA、NA和5-HT水平来影响神经内分泌免疫的网络。表明二蒽酮类可能影响血管加压素对肾上腺的作用，降低GC释放量使免疫过程的各个环节的抑制状态缓解，也可能影响垂体，通过ACTH水平降低来降低肾上腺皮质激素含量从而缓解抑制免疫状态，或者通过提高机体内DA的水平来抑制B细胞而增强T细胞和巨噬细胞的功能，从而使机体免疫功能恢复。
6.二蒽酮类白蛋白包合物的制备。采用去溶剂化-交联法制备二蒽酮类白蛋白包合物，并对其处方工艺进行优化，同时分析其形态，粒径及电位，测定其产率、包封率和载药量，并对其体外释放进行评价，得此包合物最佳制备工艺为：白蛋白加入量为1.5g，交联时间为24h，戊二醛用量为15μL，pH为9，乙醇滴加速度为1.0mL/min。其形态为球形，大小均一，平均粒径为122nm，电位值大于-50mv。产率、包封率和载药量分别为95.5%、71.43%和4.13%。此包合物在前4d的释放量占50%以上，4d到10d时，释放量约占总量的10%-15%，大约可持续4-5d，10d到25d时，药物浓度的变化不大。表明去溶剂化-交联法是一种适合二蒽酮类白蛋白包合物制备的方法，所制备的二蒽酮类白蛋白包合物形态规整、均一，稳定性好，具有高的产率、包封率及载药量，具有一定控缓释作用。
7.二蒽酮类白蛋白包合物与免疫球蛋白G抗体的偶联。采用戊二醛法制备二蒽酮类白蛋白包合物-免疫球蛋白G抗体偶联物，并对其偶联条件进行优化，用SDS-PAGE电泳检测。得二蒽酮类白蛋白包合物-免疫球蛋白G抗体偶联物最佳制备工艺：免疫球蛋白G抗体与包合物的质量比为1：1，戊二醛用量为总溶液体积的1/4，偶联时间为2h，温度为25℃，pH为中性。经SDS-PAGE电泳检测二蒽酮类白蛋白包合物-免疫球蛋白G抗体偶联物在210kDa附近有一条带。免疫球蛋白G抗体在150kDa附近有一条带，二蒽酮类白蛋白包合物在66kDa附近有一条带。这与理论上免疫球蛋白G抗体及二蒽酮类白蛋白包合物的分子量相符。表明去溶剂化-交联法是一种适合二蒽酮类白蛋白包合物制备的方法。
Hypericum extract contains numerous active compounds, each type of them have different pharmacological effects. Dianthrone is one of active compounds of Hypericum extract, including hypericin, pseudo hypericin, the original of hypericin, the original pseudo-hypericin, Central hypericin, etc. Dianthrone has many pharmacological effects such as anti-inflammatory, anti-depressants, anti-tumor and antiviral activity. There are several problems during the reasch,1. The anti-virus mechanism of Dianthrone is not clear.2. The low bioavailability of active ingredient.3. Site of action in the body is unknown. To the problems of the anti-virus mechanism, the roles of dianthrone on the immune organs, enzymes and cytokines were studied, the effects of dianthrone on the immune network were discussed, the conclusion of dianthrone antiviral mechanism was to be drawn, and which was to enhance the body's immunity. To increase the bioavailability, dianthrone was encapsulated in biodegradable materials bovine serum albumin (BSA) improving the bioavailability and effective content of dianthrone and also providing ideas for other similar active ingredients research. To clear the site of action in the body, dianthrone albumin clathrate and IgG antibodies were conjugated successfully, initial detection were conducted to provide a theoretical basis for targeted drug delivery systems. The research works were performd as follows.
1. Effects of dianthrone on immune function and antioxidant capability in mice. The thymus index, the spleen index, the activities of six enzymes(T-AOC、T-SOD、MPO、XOD、GSH-PX、POD), and the level of MDA, H2O2and NO were measured. Histopathological sections of immune organs have been observed. The following conclusions to be drawn: dianthrone had a functions to increase the spleen index, the level of T-SOD, T-AOC, GSH-PX and POD, decrease the level of MDA, NO and XOD, have no influence on the level of H2O2. The findings suggested that dianthrone could play an antioxidation activity by increasing spleen index, decreasing the level of MDA and NO, regulating activities of enzymes involved in production and elimination of free radicals in mice. The results of histopathological sections of immune organs showed that dianthrone has a repair function on the immune suppressed mice liver and spleen, and have a certain recovery on the thymus, but the effect is not obvious.
2. Effects of dianthrone on T cell surface film molecules and cytokines in serum in mice. The T cell surface film molecules(CD3、CD4、CD8、CD4/CD8) and cytokines (IL-4、IL-6、IL-10、IFN-γ、TNF-α) in serum were measured by ELISA method. The following conclusions to be drawn:dianthrone had functions to increase the T cell surface film molecules(CD3、 CD4、 CD8、 CD4/CD8) and cytokines (IFN-γand TNF-α) significantly, decrease level of IL-4、 IL-6、 IL-10. The findings suggested1dianthrone can increase the number of mature T cells, promote T cells to release cytokines, and regu the activity of Thl cells and Th2cells to increase the body's immune function.
3. Effects of dianthrone on cAMP/cGMP signaling pathway in rats. The level of cAMP and cGMP were measured by ELISA method, and the ratios of cAMP and cGMP were calculated. The following conclusions to be drawn: dianthrone had functions to increase the level of cAMP significantly, and decrease the level of cGMP and the ratios of cAMP and cGMP. The findings suggested that dianthrone can enhance the differentiation and proliferation of B lymphocytes, and promote the antibody generated to enhance the humoral immune function.
4. Effects of dianthrone on hypothalamic-pituitary-adrenal axis in rats. The level of ACTH and CORT were measured by ELISA method. The following conclusions to be drawn: dianthrone had functions to decrease the level of ACTH and CORT significantly. The findings suggested that dianthrone can decrease the level of ACTH and CORT to promote T cell transformation, reduce the hypothalamic-pituitary-adrenal axis hyperactivity to weak the dysfunction of hypothalamus, pituitary, adrenal and the effects of immunocompromised caused by HPA axis hyperactivity.
5. Effects of dianthrone on Neuroendocrine-immune network-related factor in rats.The level of IL-1, DA, NA and5-HT were measured by ELISA method, the following conclusions to be drawn: dianthrone had functions to decrease the level of IL-1, DA, NA and5-HT significantly. The findings suggested that dianthrone can affect the role of vasopressin on adrenal gland, reduce the GC release to alleviate the inhibition of the immune process. Or affect the level of ACTH in pituitary by reducing the level of Adrenal cortical hormone to alleviate the immunosuppressive. Or inhibition the function of B cells and enhanced the by increasing the level of DA torecover the immune function.
6. Preparation of dianthrone-loaded bovine serum albumin (BSA) clathrate. Used a desolvation-crosslinking method to prepare clathrate, and the prescription process was optimized. Its morphology, particle size distribution and potential distribution were estimated, the yield, encapsulation efficiency and drug loading were determined, the profile of in vitro drug release were assessed. The conditions for dianthrone-loaded bovine serum albumin clathrate preparation were optimized: the amount of albumin was1.5g, crosslinking time was24h, the amount of glutaraldehyde was15μL, pH was9, the dropping speed of ethanol was1.0mL/min. The surface morphology of the clathrate possessed smooth surfaces and spherical without any agglomeration. The mean size of the clathrate was122nm, and the zeta potential of the particles was greater than-50mV. The yield, encapsulation efficiency and drug-loading of the nanoparticles were95.5%,71.43%and4.13%, respectively. The drug release rate was greater than50%of entrapped in the BSA nanoparticles being released within4days, was10%-15%at4d to10d, and little change in drug concentration at10d to the25th day. The desolvation-crosslinking preparation method was a suitable preparation method for dianthrone albumin nanoparticles, the clathrate with a regular and uniform shape, high stability, yield, encapsulation efficiency and drug loading, and excellent controlled-release characteristics.
7. The conjunction of dianthrone albumin clathrate with IgG antibodies. Dianthrone albui clathrate and IgG antibodies were conjugated by glutaraldehyde method and optimized the conjunct conditions. The results were detected by SDS-PAGE electrophoresis. The conditions for dianthrone albumin clathrate-IgG antibody conjugates preparation were optimized: IgG antibodies and clathrate in the proportion of1:1, amount of Glutaraldehyde were1/4of the total volume of solution. Coupling time were2h, temperature were25℃and pH were neutral. Dianthrone albumin clathrate-IgG antibody conjugates were detected by SDS-PAGE electrophoresis. The results showed that dianthrone albumin clathrate-IgG antibody conjugates had a band near the210kDa, IgG antibody had a band near the150kDa, and dianthrone albumin clathrate had a band near the66kDa. The results were consistent with the theoretically molecular weight of IgG antibodies and dianthrone albumin clathrate. The glutaraldehyde method was a suitable preparation method for dianthrone albumin clathrate-IgG antibody conjugates.
引文
1.白润江，马端端，王嘉军，香菇多糖对小鼠血浆、胸腺脾脏含量的影响.西安医科大学学报，2007，18，（1）：58~59，69.
2.曹蕾，癌症新疗法—细胞因子疗法，北京：北京科学技术出版社，1993.
3.曹晓军，倪惠萍，传染性单核细胞增多症患儿T细胞亚群变化及临床意义.江苏大学学报，2007，17(5)：429~431.
4.柴田雅士，不稳定冠心病中白细胞介素-6的测定意义.国外医学临床生物化学与检验学分册，2007，18(2)：95~99.
5.陈伟，林新华，黄丽英，库拉索芦荟多糖对小鼠腹腔巨噬细胞一氧化氮生成的影响.中国现代应用药学杂志，2006，23，(1)：17~19.
6.陈杖榴，兽医药理学，北京：中国农业出版社，2007.
7.成令忠，钟翠平，蔡文琴，现代组织学，上海：上海科学技术文献出版社，2003，5：613~637.
8.程相朝，张春杰，李银聚，中药免疫增强剂对肉仔鸡免疫器官生长发育及免疫活性细胞影响的研究.中兽医学杂志，2002，(3)：6~8.
9.储茂泉，古宏晨，刘国杰，丹参酮脂质体的制备及其稳定性.中国医药工业杂志，2001，32（9）：400~404.
10.邓英杰，刘素芹，韩丽梅，黄芪多糖脂质体的制备和稳定性研究.沈阳药科大学学报，2006，13（1）：1~4.
11.丁玉玲，马淑贤，卢秀荣，人参皂甙脂质体（GSL）的研制.职业眼病杂志，2007，18，（2）：97~98.
12.董增祥，王清清，宋海峰，治疗性单克隆抗体的研究进展及其免疫偶联物的抗肿瘤应用.中国新药杂志，2008，17，(15)：1286~1289.
13.范少光，神经内分泌和免疫系统间的关系.生理科学进展，2007，3：213~217.
14.符华林，中药调节动物免疫作用的研究新进展.兽药与饲料添加剂,2002，(4)：30~34.
15.高维娟，许顺江，丛斌，CCK-8抗炎作用中DAG-PKC信号通路对cAMP-PKA信号通路的影响.中国药理学通报，2008，24（9）：1156~1160.
16.谷新利，中药免疫增强剂对雏鸡免疫功能的影响.中国兽医科技，2008，28，(2)：31~32.
17.郭乃丽，苗明三，大枣多糖对气血双虚模型小鼠全血细胞和血清粒-巨噬细胞集落刺激因子水平的影响.中国临床康复，2006，10，（27）：196~199.
18.贺建华，王建辉.中草药饲料添加剂在动物生产中的应用研究.饲料工业，2006，27(18)：1~6.
19.胡庭俊，陈炅然，山豆根多糖的自由基药理学研究.中兽医医药杂志，2005，(24)：53~58.
20.黄国平，温其标，罗志刚，微乳技术在食品化学中的应用.食品技术，2003，(01)：7~10.
21.黄园，侯世祥，林江宇，草乌肝靶向白蛋白微球的制剂学研究.中国中药杂志，1999，24，(12)：731~733.
22.黄一帆，天然物免疫促进剂和调节剂开发应用研究展望.福建畜牧兽医，1999，(1)：37~38.
23.纪竹生，刘买利，胡继明，药物配体与生物大分子受体相互作用核磁共振的研究进展.分析化学，2004，32(11)：1532-1537.
24.贾敏，周玲玲，郭胜伟，芦荟多糖对小鼠脾淋巴细胞增殖及产生IL-的影响.南京中医药大学学报，2006，22，(2)：89~90.
25.李凤前，陆彬，陈文彬，汉防己甲素缓释微囊肺靶向给药系统的研究.药学学报，2001，36，(3)：220~223.
26.李萍，曹建平，赵丽娟，类风湿关节炎患者血清TNF，IL-6水平及意义.上海免疫学杂志，2008，18(6)：368~371.
27.李晓玉，李俊，免疫药理学新论，北京：人民卫生出版社，2004.
28.李雄伟，严昌红，周成德，功能高分子微球研究无乳化剂乳液聚合法合成苯乙烯-苯乙烯磺酸钠胶乳微球.功能高分子学报,2009，2(4)：267~269.
29.李越中，药物微生物技术，北京：化学工业出版社，2004.
30.梁军，汤小芳,，魏小龙，绞股蓝总皂甙对Lewis肺癌荷瘤小鼠肿瘤生长及免疫功能的影响.药学实践杂志，2009，17，(5)：279~281.
31.凌云，单晶，张雅琳，中药蒲公英对小鼠脾淋巴细胞增殖的影响.解放军药学学报，2005，25，(1)：73~74.
32.刘晓华，张钧寿，李纯球，中药结肠靶向给药研究.中成药，2001，23，(12)：859~852.
33.刘衍兴，郭辉，小檗碱及其脂质体降血糖作用实验研究.基层中药杂志，2009，13（1）：18~19.
34.刘永春，胡之德，药物与蛋白质相互作用的荧光光谱法研究概述.宝鸡文理学院学报，2005，25，(1)：42~49.
35.吕昌龙，医学免疫学，北京：高等教育出版社，2008.
36.马庆华，张钲，白锋，髓过氧化物酶活性升高在急性冠状动脉综合征患者中的临床意义.中国心血管杂志，2005，10，(2)：101~103.
37.孟紫强，白巨利，二氧化硫吸入对小鼠9种脏器谷胱甘肽过氧化物酶活性的影响.环境与职业医学，2003，20，(1)：6~9.
38.祁超，李伟国，张玉静，圆二色谱和紫外可见光谱研究抗体-叶琳的相互作用.分析化学，2002，30，(5)：601~604.
39.钱江潮，传染性单核细胞增多症患儿淋巴细胞亚群的变化.温州医学院学报，2002，33(6)：405~406.
40.邱德凯，沈敏，曾民德，冬虫夏草多糖脂质体治疗慢性乙型肝炎的研究.中华消化杂志，2001，11，(2)：69~73.
41.邱广明，孙宗华，磁性高分子微球共价结合中性蛋白酶.生物医学工程学杂志，2005，12(3)：209~210.
42.邵礼铮，刘晓华，杜文清，中药浸膏复合5-Fu磁性微球在小鼠体内靶向定位的研究.中国药科大学学报，2003，24(1)：53~57.
43.石世德，郑文岭，杨太成，扶正抗癌方抑制人肺癌细胞增殖及增强LAK抑瘤活性的试验研究.中山大学学报，2000，39，(6)：229~233.
44.孙大业，郭艳林，马力更，细胞信号转导，北京：科学出版社，2000.
45.覃素华，潘军，张兵兵，大分子为载体的抗体偶联药物研究进展.中国新药杂志，2004，13，(6).488~493.
46.唐己婷，陈家旭，三种中药复方对慢性束缚应激大鼠下丘脑-垂体-肾上腺轴的调节.北京中医药大学学报，2002，25(3)：23~26.
47.田卫群，杨祥良，高秋华，纳米技术在生物医学中的应用.广药学院学报，2001，17：124~126.
48.王超，包玉双，曲凤玉，甘草对老年大鼠CAT、GSH2PX、LPO影响的实验研究.黑龙江医药科学，2000，23，(2)：6~7.
49.王福传，韩一超，张玉焕，复方中药免疫增强剂对鸡免疫器官组织形态学影响研究.兽药与饲料添加剂，2002，7，(1)：1~2.
50.王建文，中草药免疫药理作用概念.中兽医医药杂志，2001，（6）：19~21.
51.王君，任百祥，药物与蛋白相互作用的分析测试.中国新医药，2003，2，(5)：47~48.
52.王明圣，李立，罗燕，传染性单核细胞增多症患儿T细胞亚群变化及临床意义.中华妇幼临床医学杂志，2006，2(1)：38~39
53.王曙阳，金丝桃素提取方法探讨及金丝桃素蛋白复合物抗口蹄疫病毒的体外活性研究[学位论文].兰州：兰州大学，2005.
54.王亚俐，王海芳，光谱法研究苯甲酸钠与牛血清白蛋白的作用.北京大学学报，2002，38，(2)：159~163.
55.王月，肖尚友，陈华，硝基苯胺同牛血清白蛋白的相互作用及其毒性.环境化学，2004，23，(5)：529~534.
56.吴明星，利华明，李绍珍，骆驼蓬总碱及其脂质体对兔晶状体上皮细胞的抑制作用.眼科研究，2009，17（4）：275~278.
57.乌春华，吕元琦，袁悼斌，毛细管电泳法测定沙棘药物制品心达康片中的山奈酚和棚皮素.分析测试学报，2004，23，(3)：73~75.
58.吴会灵，杨觅原，张重杰，小分子与核酸相互作用的研究进展.分析化学，2004，32，(9)：1256~1261.
59.席孝贤，贺新，免疫学在中医药中的地位和作用.现代中医药，2002，(3)：13~14.
60.夏春梅，竹蒿对免疫低下小鼠免疫功能影响的实验研究[学位论文].乌鲁木齐：新疆医科大学2003.
61.肖崇厚，中药化学.上海：上海科技出版社，1996.
62.熊学敏，曹珏，康明，紫杉醇微球制备的初步研究.中国新药杂志，2001，10（7）：517~520.
63.徐慧显，李民勤，潘再群，葡聚糖磁性毫微粒固定化L-天冬酰胺酶的研究.生物化学杂志，1996，12(6)：744~746.
64.薛玉英，翁帼英，何俊峰，口服硫酸氢黄连素脂质体的研制.中国中药杂志，2005，20（12）：730~734.
65.杨峰，活血化瘀中药对细胞免疫低下小鼠的免疫功能影响.中国中医药科技，1993，1：15~20.
66.杨金菊，王继武，李永红，人白蛋白与3-氨甲基吡啶相互作用的研究.中国药学杂志，2003，38，(11)：882~885.
67.杨时成，朱家壁，梁秉文，喜树碱固体脂质包合物的研究.药学学报，2009，34，(2)：146~149.
68.杨云，张王刚，乔义超，急性白血病患者血浆IFN-γ及IL-10的测定.中华血液学杂志，2002，23(7)：371~372.
69.叶蔚，李钢，王小奇，攻下清热活血中药对重症胰腺炎大鼠胰腺肿瘤坏死因子A和白细胞介素1B基因表达的影响.中国中西医结合急救杂志，2007，14，(1)：43~46.
70.叶中绿，庞伟君，黄秀兰，EB病毒感染患儿细胞因子水平与T细胞亚群检测的临床意义.现代预防医学，2008，35(12)：2306~2308.
71.俞英，程晓伟，牛血清白蛋白与酸性品红的结合反应.分析化学，2000，28，(5)：583~586.
72.赵晓虹，金丝桃素新制剂在体外抗AIV的研究[学位论文]兰州：甘肃农业大学动物医学院，2006.
73.赵雨，徐金泽，赵大庆，二维拉曼相关光谱研究稀土离子对血红蛋白结构的影响.高等学校化学学报，2000，21，(12)：1913~1917.
74.张伯礼，陈克奇，徐宗佩，血瘀证患者单核细胞和中性粒细胞趋化游走能力变化及益气活血中药干预作用.天津中医药，2003，20，(1)：14~15.
75.张殿明，神经内分泌学，北京：中国医药科技出版社，1991.
76.张今，秦德安，陈百先，包有蓖麻毒蛋白脂质体制备、性质及毒性研究.生物化学和生物物理学报，2009，31（4）：472~474.
77.张景，张志荣，秦少荣，紫杉醇磁性长循环脂质体的研究.中国药学杂志，2003，38（7）：520~522.
78.张乐萃，王金宝，孙月平，复方中药多糖对鸡免疫器官形态学的影响.中国兽医科技，2008，28，(8)：26~28.
79.张强，李通，脂质过氧化对小鼠淋巴细胞功能的影响.中国实验临床免疫学杂志，1994，6，(3)：4~7.
80.张庆茹，中草药免疫促进作用的研究进展.中兽医医药杂志，2007，(5)：15~16.张群豪，陈可翼，贯叶连翘抗抑郁症的研究进展.中国中西医结合杂志，2002，22（11）：872~875.
81.张霞，蕨麻多糖免疫调节及抗氧化作用的研究[学位论文].兰州：甘肃农业大学，2005.
82.张霞，王玲，刘春红，麻黄、白芍复方中药改善急性加重期慢性阻塞性肺疾病患者肺功能和血清细胞因子的水平.中国临床康复，2006，10，(27)：73~75.
83.张新，项树林，崔晓燕.枸杞多糖对小鼠淋巴细胞信号系统的效应，中医中药与免疫，2007，13，(5)：289~292.
84.张雪梅，王晶，潘卫三，人参皂苷C-K静脉乳剂的制备及理化性质考察.沈阳药科大学学报，2004，21，(6)：420~425.
85.张学农，孙殿甲，李观海，去氢骆驼蓬碱脂质体的研究.中国医药工业杂志，2004，25（10）：441~445.
86.张英，王盛民，贺新怀，一氧化氮的免疫功能及中药的调节作用.陕西中医，2002，23，(12):1120~1123.
87.张志荣，路伟，肝靶向羟基喜树碱缓释毫微粒的研究.药学学报，2007，32，(3)：222~225.
88.张中冕，段方红，张明智，脂质体猪苓多糖抗肝转移癌作用的研究.胃肠学和肝病杂志，2009，8（3）：180~182
89.郑荣梁,黄中洋,自由基医学与农学基础,北京：高等教育出版社,2002.
90.朱海云,刘振堂,李兴华,土贝母皂甙微囊的特性及其用于肾动脉栓塞的实验研究.中华放射学杂志,2001,5(2)：107-109
91.朱深银,周远大,刘庆山,黄嘌呤氧化酶抑制剂高通量筛选模型的建立及应用.中国药学杂志,2007,42,(3)：187-189.
92. Alexander H, Schmidt B, Use of an on-line, precolumn photochemical reactor in high performance liquid chromatography of naphthodianthrones in Hypericum perforatum L. preparation. Journal of Chromatography A2003(87):181~187.
93. Apelgren LD, Zimmerman DL, Briggs S L, Antitum or activity of the monoclonal antibody Vincaalk aloidim munoconjugate LY203725(KS1/4-4-desacetylvinb lastine-3-carbo-hydrazide) in a nude mouse model of human ovarian cancer. Cancer Res2000,50:35~40.
94. Bangham A D, Standish M M, Watkins J C, Diffusion of univalentions across the lamellae of swollen phospholipid. Mol Biol2008,13,(1):238-252.
95. Bennett D. A., Phun L., Polk J. F., Voglino S. A., Zlotnik V. and Raffa R. B., Neuropharmacology of St. John's wort (Hypericum). Annals of Pharmacotherapy1998,32,(11):1201~1208.
96. Besedovsky H O, Network of immune-neuroen-docrine interaction. Clin Exp Immunol2007,27:1~12
97. Brigger I, Dubemet C, Couvreur P, Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev2002,54(5):631~651.
98. Chari R V J, Jackel K A, Bourret L A, Enhancement of the selectivity and antitumor efficacy of a CC-1065analogue through immunoconjugate formation. Cancer Res1995,55:4079~4082.
99. Cheng F, Li C Z, Preparation and the release properties of mitomycin-loaded album inmicrospheres in vitro. East Chin Univ SciTec2006,32(2):184~187.
100. Cohen P. A., Hudson J. B. and Towers G. H. N., Antiviral activities of anthraquinones, bianthrones and dianthrone derivatives from lichens. Cellular and Molecular Life Sciences2006,52,(2):180~183.
101. Decker T, Muller M, Stockinger S, The yin and yang of type1interferon activity in bacterial infection. Nat Rev Immunol2005,19:1~13.
102. Deng X.M., Li X.H., Yuan M.L., Xiong C.D., Huang Z.T., Jia W.X., Zhang Y.H., Optimisation of preparative conditions for poly-DL-lactide-polyethylene glycol microspheres with entrapped Vibrio Cholera antigens. Control Release2009,58:123~131.
103. Dolman S, Hrmsen G, Storm W E, Drug targeting to the kidney:Advances in the active targeting of therapeutics toproximal tubular cells. Advanced Drug Delivery Reviews2010,62,(14)1344~1348.
104. El-Samaligy M S, Rohdewald P., Reconstituted collagen nanoparticles-a novel drug carrier delivery system. Pharm Pharmacol2003,35:537~546.
105. Gao W J, Xu S J, Cong BStudy on the inhibitory effects of CCK-8on NF-κ β activities stimula by LPS inratPIMs.ChinJPatho-physiol2006,22(10):1891~1895.
106. Garti N, Aserin A, Fanun M. Non-ionic sucrose esters microemulsion for food applications. Part I: water solubilization. J of Colloids and Surfaces2002,164:27~37.
107. Garti N, Clement V, Leser M, Sucrose ester microemulsion.Molecular Liquids2009,80:253~296.
108. Goebel M U, Baase J, Pithan V, Acute interferon beta-lb administrationalters hypothalamic-pituitary-adrenal axis activity, plasma cytokines and leukocyte distribution in healthy subjects. Psychoneuroendocrinology2002,27:881~892.
109. Goshen I, Yirmiya R, Iverfeldt K, The role of endogenous interleukin-1in stress-Induced adrenalactivation and adrenalectomy-inducedadreno-corticotropic hormone hypersecretion. Endocrinology2003,144:4453~4458.
110. Gregoriadis G, Ryman B E, Fate of protein-containing liposomes injected into rats:An approach to the treatment of storage diseases. Eur. Biochem2002,24:485~491.
111. Gregoriadis G, Engineering liposomes for drug delivery: progress and problem. Trends Biotechnol1995,13:527~537.
112. Groux H, Bigler M, Devries J E, Inhibitory and stimulatory effects of IL-10on human CD8+T cells. Immunol2008,160:3188~3193.
113. Han S B, Kim Y H, Lee C W, Park S M, Lee H Y, Ahn K S, Characteristic immunostimulation by angelan isolated from Angelica gigas Nakai. Immunopharmacology2008,40:39~48.
114. Holsboer F, Prospects for antidepressant drug discovery. BiolPsychol2001,57(3):47~65.
115. Janeway C A, Bottomly K. Signals and signs for lymphocyte responses. Cell,2004:76:275~280.
116. Jefferey D P, Leonore A H, Kristine V, Glutathione level in antigen-presenting cells modulate Thl versus Th2response patterns. Immunology2008,95:3071~3076.
117. Jeffery H., Davis S.S., O'Hagan D.T, The preparation and characterization of poly (lactide-co-glycolide) microparticles. II. The entrapment of a model protein using a (water-in-oil)-in-water emulsion solvent evaporation technique. Pharm. Res2003,10:362~368.
118. Joshua A H, Theresa M F, Dave W M, Quantitative assessment of neurite outgrowth in human embryonic stemcell derived HN2? cells using automated high content image analysis. Neuro Toxicology2010,31,(3),277~281.
119. Kan P, Chen Z B, Lee C J, Development of nonionic surfacetant of phospholipids of wemulsion as a paclitaxel delivery system. Controlled Release1999,58,(3):271~276.
120. Karel U, Vladimr, Structural and chemical aspects of HP-MA copolymers as drug carriers. Advanced Drug Delivery Reviews2010,62,(2):150~154.
121. Karim Hosnia, Kamel Msaadaa, Bioactive components of three Hypericum species from Tunisia: A comparative study. Industrial Crops and Products2010,31:158~163.
122. Karmer P A, Receptor-mediated magnetic carriers:basis for targeting. Pharm Sci2007,(63):1646~1648.
123. Kimura H., Harris M. S., Sakamoto T., Gopalakrishna R., Gundimeda U., Cui J. Z., Spee Hinton D. R. and Ryan S. J., Dianthrone inhibits choroidal endothelial cell proliferation and c formation in vitro. Current Eye Research2007,16,(10):967~972.
124. Kratz F, Beyer U, Roth T, Transferrin conjugates ofdoxorubicin:synthesis, characterization, cellular uptake, and in vitro efficacy. Pharm Sci2008,87:338~341.
125. Langer K, Balthasa S, Vogel V, Optimization of the preparation process for human serum album in (HSA) nanoparticles. Int J Pharm2003,257(1-2):169~180.
126. Lenard J, Rabson A, Vanderoef R, Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using dianthrone and rose bengal:inhibition of fusion and syncytia formation. Proc NatlAcad Sci U S A2009,90:158~162.
127. Linde K, Ramirez G, Mulrow C D, Pauls A, Weidenhammer W, Melchart D., St. John's wort for depressionan overview and meta-analysis of randomized clinical trials. BMJ2006,313:253~261.
128. Lu B, Research development of targeting drug delivery system. China Pharmacist1998,1:1~17.
129. Lubbe A S, Bergemann C, Huhnt W, Preclinical experiences with magnetic drug targeting tolerance and efficancy.Cancer Res2006;56(20):4694~4698.
130. Mehta R.C., Jeyanthi R., Calis S., Thanoo B.C., Burton K.W., DeLuca P.P, Biodegradable microspheres as depot system for parental delivery of peptide drugs. Control Release2004,29:375～9.
131. Mehta R.C., Thanoo B.C., DeLuca P.P, Peptide containing microspheres from low molecular mass and hydrophilic poly (D, L-lactide-co-glycolide). Control Release2008,41:249~257.
132. Miller S, A natural mood booster. Newsweek2007,5:74~79.
133. Moghimi S. M., Hunter A. C., Murray J. C, Long-circulating and target specific nanoparticles: Theory to practice. Pharmacological Reviews2001,58:283~291.
134. Mosmann T R, Coffman R L, Heterogeneity of cytokine secretion patterns and functions of helper T cells. Advance Immunol2009,46:111~181.
135. Noelle R J, Marshall L, Roy M, Shepherd D M, Stamenkovic I, Ledbetter J A, Role of contact and soluble factors in the growth and differentiation of B cells by helper T cells. Adv Exp Med Biol1992,323:131~138.
136. Nubgyela A, Torio A, Muro M, Implication of soluble and membrane HLA class I and serum IL-10in liver graft acceptance. Hum Immunol2009,60:500~507.
137. Ogra Y, Curna T, Shanhid M, Feasibility of target drug delivery to selective areas of the retina. Invest Ophthalmlvis Sci2007,32,(112):2351~2355.
138. Okamoto K, Yamaguchi T, Otsuji E, Targeted chemotherapy in mice with peritoneally disseminated gastric cancer using monoclonal antibody drug conjugate. Cancer Letter2008,122:231~235.
139. Ottaviane E, Franchini A, Genedani S, ACTH and its immuneneuroen docrine functions Acomparative study. Curr Pham Des1999,5,(9):673~681.
140. Pan X., Yu S., Yao P., Shao Z, Self-assembly of b-casein and lysozyme. Journal of Colloid and Interface Science2007,316(2):405~412.
141. P K Epling-Burnette, Bin Zhong, Fanqi Bai, Cooperative regulation of Mcl-1byjanuskinase/ST and phosphatidy linositol3-kinase contribute to granulocyte-macrophagecolony-stimula(?) factor-delayed apoptosis in human neutrophils. The Journal of Immunology2001,166,(12):74~86.
142. PU Xiu-ying, LIANG Jian-ping, SHANG Ruo-feng, Influence of Hypericum perforatum Extract on Piglet Infected with Porcine Respiratory and Reproductive Syndrome Virus. Agricultural Sciences in China2009,8(6):730~739.
143. Rahimnejad, M., Jahanshahi M., Najafpour G. D., Production of biological nanoparticles from bovine serum albumin for drug delivery. African Journal of Biotechnology2006,5(20):1918~1923.
144. Raina R., Joginder Singh, Dianthrone accumulation in glands of Hypericum perforatum Linn. Current science2008,89:1981~1982.
145. Reternon T C, Isbrucher R A, Fibroproliferation in Liver disease:role of monocyte facfor. Hepatology1992,15(2):191~195.
146. Rhaese S., von Briesen H., Rubsamen-Waigmann H., Kreuter J., Langer K, Human serum albumin-polyethyleneimine nanoparticles for gene delivery. Journal of Controlled Release2003,92(1-2),199~208.
147. Selzman C H, Shames B D, Miller S A, Therapeutic implication of insurgical disease. Shock1998,10:309~413.
148. Su Y, Huang X, Raskovalova T, Cooperation of adenosine and prosta-glandin E2(PGE2) in amplification of cAMP-PKA signaling and immunosuppression. Cancer Immunol Immunoter2008,57(11):1611~1623.
149. Whort A R, Montsomery M E, Kent R S, Effect of hydrogen peroxide on Prostaglandin Produetion and cellular integrity in cultured Porcineaortic endothial cells. Clin Incest2005,76:295~302.
150. Williams L M, Ricchetti G, Sarma U, Smallie T, Foxwell B M, Interleukin-10suppression of myeloid cell activation-a continuing puzzle. Immunology2004,113:281~284.
151. Yamazaki K, Yano T, Kameyama T, Clinical significance of serum TH1/TH2cytokines in patients with pulmonary adenocarcinora. Surgery2002,131(1):236~241.
152. Zhu Z, KralovecJ, inhibition of epstein-Barr-virus—transformed human chornic lymphoeytic leukaemic B cells with monoclonal antibody yadriamycin(doxorubicin) conjugates. Cancer Immunol Immunother2005,40,(4):257~267.
2.曹蕾，癌症新疗法—细胞因子疗法，北京：北京科学技术出版社，1993.
3.曹晓军，倪惠萍，传染性单核细胞增多症患儿T细胞亚群变化及临床意义.江苏大学学报，2007，17(5)：429~431.
4.柴田雅士，不稳定冠心病中白细胞介素-6的测定意义.国外医学临床生物化学与检验学分册，2007，18(2)：95~99.
5.陈伟，林新华，黄丽英，库拉索芦荟多糖对小鼠腹腔巨噬细胞一氧化氮生成的影响.中国现代应用药学杂志，2006，23，(1)：17~19.
6.陈杖榴，兽医药理学，北京：中国农业出版社，2007.
7.成令忠，钟翠平，蔡文琴，现代组织学，上海：上海科学技术文献出版社，2003，5：613~637.
8.程相朝，张春杰，李银聚，中药免疫增强剂对肉仔鸡免疫器官生长发育及免疫活性细胞影响的研究.中兽医学杂志，2002，(3)：6~8.
9.储茂泉，古宏晨，刘国杰，丹参酮脂质体的制备及其稳定性.中国医药工业杂志，2001，32（9）：400~404.
10.邓英杰，刘素芹，韩丽梅，黄芪多糖脂质体的制备和稳定性研究.沈阳药科大学学报，2006，13（1）：1~4.
11.丁玉玲，马淑贤，卢秀荣，人参皂甙脂质体（GSL）的研制.职业眼病杂志，2007，18，（2）：97~98.
12.董增祥，王清清，宋海峰，治疗性单克隆抗体的研究进展及其免疫偶联物的抗肿瘤应用.中国新药杂志，2008，17，(15)：1286~1289.
13.范少光，神经内分泌和免疫系统间的关系.生理科学进展，2007，3：213~217.
14.符华林，中药调节动物免疫作用的研究新进展.兽药与饲料添加剂,2002，(4)：30~34.
15.高维娟，许顺江，丛斌，CCK-8抗炎作用中DAG-PKC信号通路对cAMP-PKA信号通路的影响.中国药理学通报，2008，24（9）：1156~1160.
16.谷新利，中药免疫增强剂对雏鸡免疫功能的影响.中国兽医科技，2008，28，(2)：31~32.
17.郭乃丽，苗明三，大枣多糖对气血双虚模型小鼠全血细胞和血清粒-巨噬细胞集落刺激因子水平的影响.中国临床康复，2006，10，（27）：196~199.
18.贺建华，王建辉.中草药饲料添加剂在动物生产中的应用研究.饲料工业，2006，27(18)：1~6.
19.胡庭俊，陈炅然，山豆根多糖的自由基药理学研究.中兽医医药杂志，2005，(24)：53~58.
20.黄国平，温其标，罗志刚，微乳技术在食品化学中的应用.食品技术，2003，(01)：7~10.
21.黄园，侯世祥，林江宇，草乌肝靶向白蛋白微球的制剂学研究.中国中药杂志，1999，24，(12)：731~733.
22.黄一帆，天然物免疫促进剂和调节剂开发应用研究展望.福建畜牧兽医，1999，(1)：37~38.
23.纪竹生，刘买利，胡继明，药物配体与生物大分子受体相互作用核磁共振的研究进展.分析化学，2004，32(11)：1532-1537.
24.贾敏，周玲玲，郭胜伟，芦荟多糖对小鼠脾淋巴细胞增殖及产生IL-的影响.南京中医药大学学报，2006，22，(2)：89~90.
25.李凤前，陆彬，陈文彬，汉防己甲素缓释微囊肺靶向给药系统的研究.药学学报，2001，36，(3)：220~223.
26.李萍，曹建平，赵丽娟，类风湿关节炎患者血清TNF，IL-6水平及意义.上海免疫学杂志，2008，18(6)：368~371.
27.李晓玉，李俊，免疫药理学新论，北京：人民卫生出版社，2004.
28.李雄伟，严昌红，周成德，功能高分子微球研究无乳化剂乳液聚合法合成苯乙烯-苯乙烯磺酸钠胶乳微球.功能高分子学报,2009，2(4)：267~269.
29.李越中，药物微生物技术，北京：化学工业出版社，2004.
30.梁军，汤小芳,，魏小龙，绞股蓝总皂甙对Lewis肺癌荷瘤小鼠肿瘤生长及免疫功能的影响.药学实践杂志，2009，17，(5)：279~281.
31.凌云，单晶，张雅琳，中药蒲公英对小鼠脾淋巴细胞增殖的影响.解放军药学学报，2005，25，(1)：73~74.
32.刘晓华，张钧寿，李纯球，中药结肠靶向给药研究.中成药，2001，23，(12)：859~852.
33.刘衍兴，郭辉，小檗碱及其脂质体降血糖作用实验研究.基层中药杂志，2009，13（1）：18~19.
34.刘永春，胡之德，药物与蛋白质相互作用的荧光光谱法研究概述.宝鸡文理学院学报，2005，25，(1)：42~49.
35.吕昌龙，医学免疫学，北京：高等教育出版社，2008.
36.马庆华，张钲，白锋，髓过氧化物酶活性升高在急性冠状动脉综合征患者中的临床意义.中国心血管杂志，2005，10，(2)：101~103.
37.孟紫强，白巨利，二氧化硫吸入对小鼠9种脏器谷胱甘肽过氧化物酶活性的影响.环境与职业医学，2003，20，(1)：6~9.
38.祁超，李伟国，张玉静，圆二色谱和紫外可见光谱研究抗体-叶琳的相互作用.分析化学，2002，30，(5)：601~604.
39.钱江潮，传染性单核细胞增多症患儿淋巴细胞亚群的变化.温州医学院学报，2002，33(6)：405~406.
40.邱德凯，沈敏，曾民德，冬虫夏草多糖脂质体治疗慢性乙型肝炎的研究.中华消化杂志，2001，11，(2)：69~73.
41.邱广明，孙宗华，磁性高分子微球共价结合中性蛋白酶.生物医学工程学杂志，2005，12(3)：209~210.
42.邵礼铮，刘晓华，杜文清，中药浸膏复合5-Fu磁性微球在小鼠体内靶向定位的研究.中国药科大学学报，2003，24(1)：53~57.
43.石世德，郑文岭，杨太成，扶正抗癌方抑制人肺癌细胞增殖及增强LAK抑瘤活性的试验研究.中山大学学报，2000，39，(6)：229~233.
44.孙大业，郭艳林，马力更，细胞信号转导，北京：科学出版社，2000.
45.覃素华，潘军，张兵兵，大分子为载体的抗体偶联药物研究进展.中国新药杂志，2004，13，(6).488~493.
46.唐己婷，陈家旭，三种中药复方对慢性束缚应激大鼠下丘脑-垂体-肾上腺轴的调节.北京中医药大学学报，2002，25(3)：23~26.
47.田卫群，杨祥良，高秋华，纳米技术在生物医学中的应用.广药学院学报，2001，17：124~126.
48.王超，包玉双，曲凤玉，甘草对老年大鼠CAT、GSH2PX、LPO影响的实验研究.黑龙江医药科学，2000，23，(2)：6~7.
49.王福传，韩一超，张玉焕，复方中药免疫增强剂对鸡免疫器官组织形态学影响研究.兽药与饲料添加剂，2002，7，(1)：1~2.
50.王建文，中草药免疫药理作用概念.中兽医医药杂志，2001，（6）：19~21.
51.王君，任百祥，药物与蛋白相互作用的分析测试.中国新医药，2003，2，(5)：47~48.
52.王明圣，李立，罗燕，传染性单核细胞增多症患儿T细胞亚群变化及临床意义.中华妇幼临床医学杂志，2006，2(1)：38~39
53.王曙阳，金丝桃素提取方法探讨及金丝桃素蛋白复合物抗口蹄疫病毒的体外活性研究[学位论文].兰州：兰州大学，2005.
54.王亚俐，王海芳，光谱法研究苯甲酸钠与牛血清白蛋白的作用.北京大学学报，2002，38，(2)：159~163.
55.王月，肖尚友，陈华，硝基苯胺同牛血清白蛋白的相互作用及其毒性.环境化学，2004，23，(5)：529~534.
56.吴明星，利华明，李绍珍，骆驼蓬总碱及其脂质体对兔晶状体上皮细胞的抑制作用.眼科研究，2009，17（4）：275~278.
57.乌春华，吕元琦，袁悼斌，毛细管电泳法测定沙棘药物制品心达康片中的山奈酚和棚皮素.分析测试学报，2004，23，(3)：73~75.
58.吴会灵，杨觅原，张重杰，小分子与核酸相互作用的研究进展.分析化学，2004，32，(9)：1256~1261.
59.席孝贤，贺新，免疫学在中医药中的地位和作用.现代中医药，2002，(3)：13~14.
60.夏春梅，竹蒿对免疫低下小鼠免疫功能影响的实验研究[学位论文].乌鲁木齐：新疆医科大学2003.
61.肖崇厚，中药化学.上海：上海科技出版社，1996.
62.熊学敏，曹珏，康明，紫杉醇微球制备的初步研究.中国新药杂志，2001，10（7）：517~520.
63.徐慧显，李民勤，潘再群，葡聚糖磁性毫微粒固定化L-天冬酰胺酶的研究.生物化学杂志，1996，12(6)：744~746.
64.薛玉英，翁帼英，何俊峰，口服硫酸氢黄连素脂质体的研制.中国中药杂志，2005，20（12）：730~734.
65.杨峰，活血化瘀中药对细胞免疫低下小鼠的免疫功能影响.中国中医药科技，1993，1：15~20.
66.杨金菊，王继武，李永红，人白蛋白与3-氨甲基吡啶相互作用的研究.中国药学杂志，2003，38，(11)：882~885.
67.杨时成，朱家壁，梁秉文，喜树碱固体脂质包合物的研究.药学学报，2009，34，(2)：146~149.
68.杨云，张王刚，乔义超，急性白血病患者血浆IFN-γ及IL-10的测定.中华血液学杂志，2002，23(7)：371~372.
69.叶蔚，李钢，王小奇，攻下清热活血中药对重症胰腺炎大鼠胰腺肿瘤坏死因子A和白细胞介素1B基因表达的影响.中国中西医结合急救杂志，2007，14，(1)：43~46.
70.叶中绿，庞伟君，黄秀兰，EB病毒感染患儿细胞因子水平与T细胞亚群检测的临床意义.现代预防医学，2008，35(12)：2306~2308.
71.俞英，程晓伟，牛血清白蛋白与酸性品红的结合反应.分析化学，2000，28，(5)：583~586.
72.赵晓虹，金丝桃素新制剂在体外抗AIV的研究[学位论文]兰州：甘肃农业大学动物医学院，2006.
73.赵雨，徐金泽，赵大庆，二维拉曼相关光谱研究稀土离子对血红蛋白结构的影响.高等学校化学学报，2000，21，(12)：1913~1917.
74.张伯礼，陈克奇，徐宗佩，血瘀证患者单核细胞和中性粒细胞趋化游走能力变化及益气活血中药干预作用.天津中医药，2003，20，(1)：14~15.
75.张殿明，神经内分泌学，北京：中国医药科技出版社，1991.
76.张今，秦德安，陈百先，包有蓖麻毒蛋白脂质体制备、性质及毒性研究.生物化学和生物物理学报，2009，31（4）：472~474.
77.张景，张志荣，秦少荣，紫杉醇磁性长循环脂质体的研究.中国药学杂志，2003，38（7）：520~522.
78.张乐萃，王金宝，孙月平，复方中药多糖对鸡免疫器官形态学的影响.中国兽医科技，2008，28，(8)：26~28.
79.张强，李通，脂质过氧化对小鼠淋巴细胞功能的影响.中国实验临床免疫学杂志，1994，6，(3)：4~7.
80.张庆茹，中草药免疫促进作用的研究进展.中兽医医药杂志，2007，(5)：15~16.张群豪，陈可翼，贯叶连翘抗抑郁症的研究进展.中国中西医结合杂志，2002，22（11）：872~875.
81.张霞，蕨麻多糖免疫调节及抗氧化作用的研究[学位论文].兰州：甘肃农业大学，2005.
82.张霞，王玲，刘春红，麻黄、白芍复方中药改善急性加重期慢性阻塞性肺疾病患者肺功能和血清细胞因子的水平.中国临床康复，2006，10，(27)：73~75.
83.张新，项树林，崔晓燕.枸杞多糖对小鼠淋巴细胞信号系统的效应，中医中药与免疫，2007，13，(5)：289~292.
84.张雪梅，王晶，潘卫三，人参皂苷C-K静脉乳剂的制备及理化性质考察.沈阳药科大学学报，2004，21，(6)：420~425.
85.张学农，孙殿甲，李观海，去氢骆驼蓬碱脂质体的研究.中国医药工业杂志，2004，25（10）：441~445.
86.张英，王盛民，贺新怀，一氧化氮的免疫功能及中药的调节作用.陕西中医，2002，23，(12):1120~1123.
87.张志荣，路伟，肝靶向羟基喜树碱缓释毫微粒的研究.药学学报，2007，32，(3)：222~225.
88.张中冕，段方红，张明智，脂质体猪苓多糖抗肝转移癌作用的研究.胃肠学和肝病杂志，2009，8（3）：180~182
89.郑荣梁,黄中洋,自由基医学与农学基础,北京：高等教育出版社,2002.
90.朱海云,刘振堂,李兴华,土贝母皂甙微囊的特性及其用于肾动脉栓塞的实验研究.中华放射学杂志,2001,5(2)：107-109
91.朱深银,周远大,刘庆山,黄嘌呤氧化酶抑制剂高通量筛选模型的建立及应用.中国药学杂志,2007,42,(3)：187-189.
92. Alexander H, Schmidt B, Use of an on-line, precolumn photochemical reactor in high performance liquid chromatography of naphthodianthrones in Hypericum perforatum L. preparation. Journal of Chromatography A2003(87):181~187.
93. Apelgren LD, Zimmerman DL, Briggs S L, Antitum or activity of the monoclonal antibody Vincaalk aloidim munoconjugate LY203725(KS1/4-4-desacetylvinb lastine-3-carbo-hydrazide) in a nude mouse model of human ovarian cancer. Cancer Res2000,50:35~40.
94. Bangham A D, Standish M M, Watkins J C, Diffusion of univalentions across the lamellae of swollen phospholipid. Mol Biol2008,13,(1):238-252.
95. Bennett D. A., Phun L., Polk J. F., Voglino S. A., Zlotnik V. and Raffa R. B., Neuropharmacology of St. John's wort (Hypericum). Annals of Pharmacotherapy1998,32,(11):1201~1208.
96. Besedovsky H O, Network of immune-neuroen-docrine interaction. Clin Exp Immunol2007,27:1~12
97. Brigger I, Dubemet C, Couvreur P, Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev2002,54(5):631~651.
98. Chari R V J, Jackel K A, Bourret L A, Enhancement of the selectivity and antitumor efficacy of a CC-1065analogue through immunoconjugate formation. Cancer Res1995,55:4079~4082.
99. Cheng F, Li C Z, Preparation and the release properties of mitomycin-loaded album inmicrospheres in vitro. East Chin Univ SciTec2006,32(2):184~187.
100. Cohen P. A., Hudson J. B. and Towers G. H. N., Antiviral activities of anthraquinones, bianthrones and dianthrone derivatives from lichens. Cellular and Molecular Life Sciences2006,52,(2):180~183.
101. Decker T, Muller M, Stockinger S, The yin and yang of type1interferon activity in bacterial infection. Nat Rev Immunol2005,19:1~13.
102. Deng X.M., Li X.H., Yuan M.L., Xiong C.D., Huang Z.T., Jia W.X., Zhang Y.H., Optimisation of preparative conditions for poly-DL-lactide-polyethylene glycol microspheres with entrapped Vibrio Cholera antigens. Control Release2009,58:123~131.
103. Dolman S, Hrmsen G, Storm W E, Drug targeting to the kidney:Advances in the active targeting of therapeutics toproximal tubular cells. Advanced Drug Delivery Reviews2010,62,(14)1344~1348.
104. El-Samaligy M S, Rohdewald P., Reconstituted collagen nanoparticles-a novel drug carrier delivery system. Pharm Pharmacol2003,35:537~546.
105. Gao W J, Xu S J, Cong BStudy on the inhibitory effects of CCK-8on NF-κ β activities stimula by LPS inratPIMs.ChinJPatho-physiol2006,22(10):1891~1895.
106. Garti N, Aserin A, Fanun M. Non-ionic sucrose esters microemulsion for food applications. Part I: water solubilization. J of Colloids and Surfaces2002,164:27~37.
107. Garti N, Clement V, Leser M, Sucrose ester microemulsion.Molecular Liquids2009,80:253~296.
108. Goebel M U, Baase J, Pithan V, Acute interferon beta-lb administrationalters hypothalamic-pituitary-adrenal axis activity, plasma cytokines and leukocyte distribution in healthy subjects. Psychoneuroendocrinology2002,27:881~892.
109. Goshen I, Yirmiya R, Iverfeldt K, The role of endogenous interleukin-1in stress-Induced adrenalactivation and adrenalectomy-inducedadreno-corticotropic hormone hypersecretion. Endocrinology2003,144:4453~4458.
110. Gregoriadis G, Ryman B E, Fate of protein-containing liposomes injected into rats:An approach to the treatment of storage diseases. Eur. Biochem2002,24:485~491.
111. Gregoriadis G, Engineering liposomes for drug delivery: progress and problem. Trends Biotechnol1995,13:527~537.
112. Groux H, Bigler M, Devries J E, Inhibitory and stimulatory effects of IL-10on human CD8+T cells. Immunol2008,160:3188~3193.
113. Han S B, Kim Y H, Lee C W, Park S M, Lee H Y, Ahn K S, Characteristic immunostimulation by angelan isolated from Angelica gigas Nakai. Immunopharmacology2008,40:39~48.
114. Holsboer F, Prospects for antidepressant drug discovery. BiolPsychol2001,57(3):47~65.
115. Janeway C A, Bottomly K. Signals and signs for lymphocyte responses. Cell,2004:76:275~280.
116. Jefferey D P, Leonore A H, Kristine V, Glutathione level in antigen-presenting cells modulate Thl versus Th2response patterns. Immunology2008,95:3071~3076.
117. Jeffery H., Davis S.S., O'Hagan D.T, The preparation and characterization of poly (lactide-co-glycolide) microparticles. II. The entrapment of a model protein using a (water-in-oil)-in-water emulsion solvent evaporation technique. Pharm. Res2003,10:362~368.
118. Joshua A H, Theresa M F, Dave W M, Quantitative assessment of neurite outgrowth in human embryonic stemcell derived HN2? cells using automated high content image analysis. Neuro Toxicology2010,31,(3),277~281.
119. Kan P, Chen Z B, Lee C J, Development of nonionic surfacetant of phospholipids of wemulsion as a paclitaxel delivery system. Controlled Release1999,58,(3):271~276.
120. Karel U, Vladimr, Structural and chemical aspects of HP-MA copolymers as drug carriers. Advanced Drug Delivery Reviews2010,62,(2):150~154.
121. Karim Hosnia, Kamel Msaadaa, Bioactive components of three Hypericum species from Tunisia: A comparative study. Industrial Crops and Products2010,31:158~163.
122. Karmer P A, Receptor-mediated magnetic carriers:basis for targeting. Pharm Sci2007,(63):1646~1648.
123. Kimura H., Harris M. S., Sakamoto T., Gopalakrishna R., Gundimeda U., Cui J. Z., Spee Hinton D. R. and Ryan S. J., Dianthrone inhibits choroidal endothelial cell proliferation and c formation in vitro. Current Eye Research2007,16,(10):967~972.
124. Kratz F, Beyer U, Roth T, Transferrin conjugates ofdoxorubicin:synthesis, characterization, cellular uptake, and in vitro efficacy. Pharm Sci2008,87:338~341.
125. Langer K, Balthasa S, Vogel V, Optimization of the preparation process for human serum album in (HSA) nanoparticles. Int J Pharm2003,257(1-2):169~180.
126. Lenard J, Rabson A, Vanderoef R, Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using dianthrone and rose bengal:inhibition of fusion and syncytia formation. Proc NatlAcad Sci U S A2009,90:158~162.
127. Linde K, Ramirez G, Mulrow C D, Pauls A, Weidenhammer W, Melchart D., St. John's wort for depressionan overview and meta-analysis of randomized clinical trials. BMJ2006,313:253~261.
128. Lu B, Research development of targeting drug delivery system. China Pharmacist1998,1:1~17.
129. Lubbe A S, Bergemann C, Huhnt W, Preclinical experiences with magnetic drug targeting tolerance and efficancy.Cancer Res2006;56(20):4694~4698.
130. Mehta R.C., Jeyanthi R., Calis S., Thanoo B.C., Burton K.W., DeLuca P.P, Biodegradable microspheres as depot system for parental delivery of peptide drugs. Control Release2004,29:375～9.
131. Mehta R.C., Thanoo B.C., DeLuca P.P, Peptide containing microspheres from low molecular mass and hydrophilic poly (D, L-lactide-co-glycolide). Control Release2008,41:249~257.
132. Miller S, A natural mood booster. Newsweek2007,5:74~79.
133. Moghimi S. M., Hunter A. C., Murray J. C, Long-circulating and target specific nanoparticles: Theory to practice. Pharmacological Reviews2001,58:283~291.
134. Mosmann T R, Coffman R L, Heterogeneity of cytokine secretion patterns and functions of helper T cells. Advance Immunol2009,46:111~181.
135. Noelle R J, Marshall L, Roy M, Shepherd D M, Stamenkovic I, Ledbetter J A, Role of contact and soluble factors in the growth and differentiation of B cells by helper T cells. Adv Exp Med Biol1992,323:131~138.
136. Nubgyela A, Torio A, Muro M, Implication of soluble and membrane HLA class I and serum IL-10in liver graft acceptance. Hum Immunol2009,60:500~507.
137. Ogra Y, Curna T, Shanhid M, Feasibility of target drug delivery to selective areas of the retina. Invest Ophthalmlvis Sci2007,32,(112):2351~2355.
138. Okamoto K, Yamaguchi T, Otsuji E, Targeted chemotherapy in mice with peritoneally disseminated gastric cancer using monoclonal antibody drug conjugate. Cancer Letter2008,122:231~235.
139. Ottaviane E, Franchini A, Genedani S, ACTH and its immuneneuroen docrine functions Acomparative study. Curr Pham Des1999,5,(9):673~681.
140. Pan X., Yu S., Yao P., Shao Z, Self-assembly of b-casein and lysozyme. Journal of Colloid and Interface Science2007,316(2):405~412.
141. P K Epling-Burnette, Bin Zhong, Fanqi Bai, Cooperative regulation of Mcl-1byjanuskinase/ST and phosphatidy linositol3-kinase contribute to granulocyte-macrophagecolony-stimula(?) factor-delayed apoptosis in human neutrophils. The Journal of Immunology2001,166,(12):74~86.
142. PU Xiu-ying, LIANG Jian-ping, SHANG Ruo-feng, Influence of Hypericum perforatum Extract on Piglet Infected with Porcine Respiratory and Reproductive Syndrome Virus. Agricultural Sciences in China2009,8(6):730~739.
143. Rahimnejad, M., Jahanshahi M., Najafpour G. D., Production of biological nanoparticles from bovine serum albumin for drug delivery. African Journal of Biotechnology2006,5(20):1918~1923.
144. Raina R., Joginder Singh, Dianthrone accumulation in glands of Hypericum perforatum Linn. Current science2008,89:1981~1982.
145. Reternon T C, Isbrucher R A, Fibroproliferation in Liver disease:role of monocyte facfor. Hepatology1992,15(2):191~195.
146. Rhaese S., von Briesen H., Rubsamen-Waigmann H., Kreuter J., Langer K, Human serum albumin-polyethyleneimine nanoparticles for gene delivery. Journal of Controlled Release2003,92(1-2),199~208.
147. Selzman C H, Shames B D, Miller S A, Therapeutic implication of insurgical disease. Shock1998,10:309~413.
148. Su Y, Huang X, Raskovalova T, Cooperation of adenosine and prosta-glandin E2(PGE2) in amplification of cAMP-PKA signaling and immunosuppression. Cancer Immunol Immunoter2008,57(11):1611~1623.
149. Whort A R, Montsomery M E, Kent R S, Effect of hydrogen peroxide on Prostaglandin Produetion and cellular integrity in cultured Porcineaortic endothial cells. Clin Incest2005,76:295~302.
150. Williams L M, Ricchetti G, Sarma U, Smallie T, Foxwell B M, Interleukin-10suppression of myeloid cell activation-a continuing puzzle. Immunology2004,113:281~284.
151. Yamazaki K, Yano T, Kameyama T, Clinical significance of serum TH1/TH2cytokines in patients with pulmonary adenocarcinora. Surgery2002,131(1):236~241.
152. Zhu Z, KralovecJ, inhibition of epstein-Barr-virus—transformed human chornic lymphoeytic leukaemic B cells with monoclonal antibody yadriamycin(doxorubicin) conjugates. Cancer Immunol Immunother2005,40,(4):257~267.