消化道的白念珠菌感染与脾虚的相关性及其免疫学机制研究
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摘要
目的:探讨小鼠在脾虚状态下对消化道感染白念珠菌的易感性及其免疫学机制。阐明脾虚小鼠对白念珠菌易感性的变化特点,以进一步控制其感染;明确脾虚小鼠感染白念珠菌前后某些免疫功能的变化及其与白念珠菌感染的关系;明确脾虚证易并发白念珠菌感染的免疫学机制,为临床防治白念珠菌感染和脾虚证提供一定的理论依据。
材料与方法:本实验将小鼠分层随机分成四组,即正常对照组(A组)、脾虚模型组(B组)、正常感染白念珠菌组(C组)、脾虚感染白念珠菌组(D组)。采用饮食失节加劳倦过度的复合因素制备小鼠脾虚证模型。模型成功后,经口灌给C、D组小鼠白念珠菌悬液,之后连续3周,观察各组小鼠的体重变化及一般状况的改变,记录并计算平均生存天数及存活率,并检测粪便及肾脏中的活白念珠菌的数量,测定小鼠脾指数及胸腺指数。取小鼠空肠作HE染色观察小鼠小肠黏膜形态的病理学改变,电镜观察小肠超微结构的变化。应用动物血液分析仪检测小鼠外周血中白细胞总数、中性粒细胞、淋巴细胞数及单核细胞数,并测定红细胞数及血红蛋白含量的改变;应用酶联免疫吸附法(ELISA)测定脾虚模型小鼠肠组织表达的免疫球蛋白A(IgA)、血清中白细胞介素1β(IL-1β)、腹腔巨噬细胞肿瘤坏死因子α(TNF-α)、脾细胞γ-干扰素(IFN-γ)及白细胞介素10(IL-10)的含量。应用逆转录/聚合酶链式反应(RT-PCR)方法检测肠组织局部IFN-γmRNA和IL-10mRNA的表达水平。
结果:
1.白念珠菌消化道感染对脾虚小鼠体重及一般状况的影响
脾虚小鼠比正常小鼠体重明显减轻(P＜0.01),且一般状况欠佳。正常小鼠感染后体重无明显变化,而脾虚感染组小鼠的体重下降明显(P＜0.01)。
2.白念珠菌消化道感染对脾虚小鼠生存天数及生存率的影响
脾虚小鼠平均生存天数缩短(P＜0.05),生存率下降至75%;正常小鼠感染白念珠菌后,平均生存天数无统计学意义。而脾虚小鼠感染后平均生存天数明显缩短(P＜0.01),生存率下降至55%。
3.白念珠菌消化道感染对脾虚小鼠粪便活菌数的影响
正常小鼠感染后,便活菌数呈先增高后减少的趋势,而脾虚小鼠感染后则呈逐渐增高趋势,并始终高于前者。在感染后第6天,两组小鼠的便活菌数有统计学意义(P＜0.05);感染后第9天、第12天、第15天及第18天,统计学差异显著(P＜0.01)。
4.白念珠菌消化道感染对脾虚小鼠肾脏内活菌数的影响
正常小鼠感染后,肾脏内活菌数相对较少,而脾虚小鼠感染后肾脏内活菌数明显增加(P＜0.01)。
5.白念珠菌消化道感染对脾虚小鼠脾指数及胸腺指数的影响
脾虚小鼠的脾脏及胸腺重量均低于正常小鼠,但无统计学意义。小鼠感染白念珠菌后期,脾指数及胸腺指数均明显增高,统计学差异显著(P＜0.05或P＜0.01),尤其是脾虚小鼠脾脏重量增加更为明显。
6.白念珠菌消化道感染对脾虚小鼠小肠黏膜形态学的影响
脾虚组小鼠小肠绒毛略变短,游离面上皮松散。正常小鼠感染后期,小肠绒毛变短且稀疏,游离面上皮立方形改变,固有膜空泡样改变,细胞轻度水肿。脾虚感染组小肠绒毛稀疏不完整,柱状上皮立方形改变,固有膜空泡样改变。
7.白念珠菌消化道感染对脾虚小鼠小肠黏膜超微结构的影响
正常小鼠感染后期,微绒毛较细疏且长短大小不一,胞质内线粒体稍肿胀,嵴较松散,部分呈空泡样改变。脾虚感染组小鼠小肠微绒毛短少且不整齐,线粒体肿胀,嵴断裂消失,呈空泡样改变,并可见内质网扩张、核糖体脱落等。
8.白念珠菌消化道感染对脾虚小鼠外周血细胞数量的影响
脾虚小鼠外周血中红细胞数及血红蛋白含量均有所降低,尤其是感染后期的脾虚小鼠下降更加明显(P＜0.01)。感染后小鼠体内白细胞数量增多,正常小鼠感染后期,淋巴细胞数明显增高(P＜0.01);而脾虚小鼠感染后期,单核细胞数增高明显(P＜0.01),中性粒细胞也明显增加。
9.白念珠菌消化道感染对脾虚小鼠腹腔巨噬细胞分泌TNF-α的影响
与正常组比较,脾虚组小鼠腹腔巨噬细胞TNF-α的分泌减少,而正常小鼠感染后期TNF-α的分泌增多,二者均有统计学差异(P＜0.05);脾虚感染组小鼠TNF-α的分泌则明显高于其它各组(P＜0.01)。
10.白念珠菌消化道感染对脾虚小鼠血清中IL-1β含量的影响
脾虚小鼠血清中IL-1β含量无明显改变;正常小鼠感染后期,IL-1β含量虽有增多,但无统计学意义;脾虚小鼠感染后期,IL-1β含量则明显升高(P＜0.01)。
11.白念珠菌消化道感染对脾虚小鼠小肠组织IgA含量的影响
脾虚小鼠比正常小鼠小肠组织IgA含量减少,差异显著(P＜0.01);小鼠感染后期,肠组织IgA分泌也呈下降趋势,特别是脾虚感染组小鼠IgA含量明显低于其它各组(P＜0.01)。
12.白念珠菌消化道感染对脾虚小鼠脾脏IFN-γ和IL-10表达的影响
正常小鼠感染后表达IFN-γ和IL-10的水平均高于正常组,但无统计学差异;而脾虚小鼠感染白念珠菌后期,则显著高于其它各组(P＜0.01)。
13.白念珠菌消化道感染对脾虚小鼠肠组织中IFN-γmRNA及IL-10mRNA表达的影响
与正常组比较,脾虚组小鼠IFN-γmRNA表达增高(P＜0.01),IL-10mRNA差异不明显;与脾虚组比较,正常与脾虚小鼠感染后肠组织表达IFN-γmRNA和IL-10mRNA的水平均显著升高(P＜0.01)。与正常感染白念珠菌组比较,脾虚小鼠感染后期IFN-γmRNA的表达水平仍处于高水平状态,有显著性差异(P＜0.01),但IL-10mRNA表达减少(P＜0.05)。
结论:
1.小鼠在脾虚状态下对消化道感染白念珠菌的易感性增强。可使脾虚小鼠体重显著下降,脾指数及胸腺指数明显增高,还可以使平均生存天数明显缩短,生存率大幅度下降,而且便活菌数持续增高,肾脏内活菌数也显著增加。
2.小鼠在脾虚状态下消化道感染白念珠菌后,导致小肠组织IgA含量明显减少,削弱了消化道局部免疫防御功能。更容易加重小肠黏膜形态学改变及小肠上皮细胞超微结构的病理变化。还可入血播散至其它部位,造成外周血中红细胞数量减少,血红蛋白含量降低,体内炎性细胞大量增殖。
3.消化道的白念珠菌感染是否致病与小鼠的免疫力密切相关,尤其是在免疫功能低下时危害更大,同时又进一步加重脾虚状态或感染的病情。脾虚小鼠在抗白念珠菌感染过程中,多种免疫细胞及细胞因子参与了免疫应答。
Purpose:To investigate the susceptibility of Candida albicans infection of alimentary tract in the state of deficiency of spleen and the immunological mechanisms.To illuminate the characteristics of change of susceptibility in deficiency of spleen,to further control their infection.To illuminate the relationship between immunological functions and Candida albicans and some immunological changes before and after the infection.To illuminate the immunological mechanisms of Candida albicans infection in the state of deficiency of spleen,for the prevention and treatment of the infection.
Material and method:The experimental mice were randomly divided into four groups,that is,the normal control group(A group),deficiency of spleen model group(B group),Candida albicans infection in normal group(C group),deficiency of spleen with Candida albicans infection group(D group).The animal model of spleen deficiency was prepared by using of irregular-feeding and overstrain methods.The mice in group C and D were fed with suspension of Candida albicans, in the following 3 weeks,mice in each group were observed changes in body weight and general condition.The average survival days and survival rate were recorded and calculated.The number of living Candida albicans in fecal and kidney was detected;spleen index and thymus index were also measured.The jejunum of the mice were prepared with HE staining method,and the morphological changes of jejunum were observed with optical microscope.Ultrastructural changes of small intestine were observed with electron microscopy.The total number of peripheral blood leukocytes,neutrophils,lymphocytes and mononuclear cells,and RBC number and hemoglobin content of the change were also measured with animal blood analyzer.The expression of immunoglobulin A(IgA),serum interleukin-1β (IL-1β),macrophage tumor necrosis factor-α(TNF-α),spleen cells fromγ-interferon(IFN-γ) and interleukin-10(IL-10) content in intestinal tissue of spleen deficiency mice were detected with application of enzyme-linked immunosorbent assay(ELISA).Using reverse transcription / polymerase chain reaction(RT-PCR) method detected the expression of IFN-γmRNA and IL-10mRNA level in the intestinal tissue.
Results:
1.Effects on body weight and general condition of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Body weight in spleen deficiency mice was significant lighter than normal mice(P＜0.01),with the addition of poor general condition.In normal mice after infection,no significant changes in body weight,and the weight of spleen deficiency infected mice decreased significantly(P＜0.01).
2.Effects on the survival days and survival rate of spleen deficiency mice with Candida albicans infection of the alimentary tract.
The survival days of spleen deficiency mice were reduced(P＜0.05),the survival rate dropped to 75%;the average survival days were no significant difference in normal mice infected with Candida albicans.And the average survival days was reduced significantly in spleen deficiency mice infected with Candida albicans,the survival rate also dropped to 55%.
3.Effects on the number of living fecal bacteria of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Normal mice after infection,the number of fecal living bacteria appeared a downward trend after an increase in initial stage,and that number shows an increasing trend,and always higher than the former in infected spleen deficiency mice.In the first six days after infection,the number of fecal living bacteria of the two groups mice have a statistically significance difference(P＜0.05); the first 9 days,12 days,the first 15 days and 18 days,both statistically significance difference(P＜0.01).
4.Effects on the number of living renal bacteria of spleen deficiency mice with Candida albicans infection of the alimentary tract.
In normal mice after infection,a relatively small number of living bacteria was observed in kidney,and that number have a marked increase in the kidney of infected spleen deficiency mice(P＜0.01).
5.Effects on the spleen index and thymus index of spleen deficiency mice with Candida albicans infection of the alimentary tract.
The weight of spleen and thymus in spleen deficiency mice was lower than that of normal mice,but not statistically significant.After Candida albicans infection in mice,the spleen index and thymus index were significantly higher, with statistically significant differences(P＜0.05 or P＜0.01).In particular, increased weight of spleen deficiency mice became more evident.
6.Effects on morphology of small intestinal submucosa of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Intestinal villi in spleen deficiency mice became slightly shorter,and scattered free surface epithelial.In normal mice after infection,intestinal villi became shorter and sparse,and free surface epithelial became cubic form; the inherent membrane had vacuole-like change with mild edema in cells.In infected spleen deficiency mice,small intestinal villi became sparse and incomplete,with cubic columnar epithelium changes,the inherent membrane had vacuole-like change.
7.Effects on ultrastructure of small intestinal submucosa of spleen deficiency mice with Candida albicans infection of the alimentary tract.
In normal mice after infection,microvilli became sparse and different in length and size,slightly swollen mitochondria in the cytoplasm,a looser ridge, and some showed vacuolated changes.In infected spleen deficiency mice, microvilli became untidily sparse and shorter,mitochondrial swelling, disappearance of ridge,vacuolated changes,and with addition of expansion of the endoplasmic reticulum and ribosome falling off,etc.
8.Effects on the number of peripheral blood cells of spleen deficiency mice with Candida albicans infection of the alimentary tract.
The number of peripheral blood hemoglobin content of red blood cells are reduced in spleen deficiency mice,especially in the mice after infection(P＜0.01).the number of leukocytes in infected spleen deficiency mice was significantly increased(P＜0.01);the number of mononuclear cells increased significantly(P＜0.01)in normal mice,and neutrophils also significantly increased.
9.Effects on the Secretion of TNF-αof peritoneal macrophages of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Compared to the normal group,the Secretion of TNF-αof peritoneal macrophages was reduced,and the infected normal mice was increased,both have significantly different(P＜0.05);the Secretion of infected spleen deficiency mice was significantly higher than other groups(P＜0.01).
10.Effects on the content of serum IL-1βof spleen deficiency mice with Candida albicans infection of the alimentary tract.
There was no significant change in serum IL-1βcontent in spleen deficiency mice;in final stage of infection in normal mice,serum IL-1βcontent increased, but without statistical significance,and in infected spleen deficiency mice, serum IL-1βcontent was significantly higher(P＜0.01).
11.Effects on IgA content of intestinal tissue of spleen deficiency mice with Candida albicans infection of the alimentary tract.
IgA content of intestinal tissue decreased significantly(P＜0.01)in spleen deficiency mice,compared to normal mice.After infection,intestinal IgA secretion also declined,especially in infected spleen deficiency mice,the IgA content was significantly lower than the other groups(P＜0.01).
12.Effects on the expression of IFN-γand IL-10 of spleen of spleen deficiency mice with Candida albicans infection of the alimentary tract.
The expression of IFN-γand IL-10 in normal mice after infection was higher than the normal group,but no significant difference;and the expression in infected spleen deficiency mice was significantly higher than the other groups (P＜0.01) in the final infectious stage.
13.Effects on the expression of IFN-γmRNA and IL-10mRNA of intestinal tissue of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Compared to the normal group,the expression of IFN-γmRNA in spleen deficiency mice was increased(P＜0.01),and that of IL-10mRNA had no obvious difference.Compared to spleen deficiency mice,the expressions of IFN-γmRNA and IL-10mRNA were both significantly increased(P＜0.01) in the other groups. Compared to infected normal groups,the expression of IFN-γmRNA was still at a high level state in final infectious stage of infected spleen deficiency mice, but the expression of IL-10mRNA was reduced(P＜0.05).
Conclusion:
1.The susceptibility of Candida albicans of mice was enhanced in a state of spleen deficiency.Which led to a significant drop in body weight,increasing of spleen index and thymus index,the shortened average number of days,the decreased survival rate,and a sustaining increasing number of living bacteria in feces and kidney.
2.After Candida albicans infection in the alimentary tract in a state of spleen deficiency,IgA content of intestinal tissue decreased significantly,leading to hypofunction of the intestinal function of local immune defense,which caused the morphological changes of intestinal mucosa and pathological changes of intestinal epithelial cell ultrastructure.Meanwhile,bacteria could be disseminated into the blood and other parts of the body,so that cause reduction in the number of red blood cells in peripheral blood,hemoglobin decreased,the proliferation of a large number of inflammatory cells in vivo.
3.Whether pathogenic or not of Candida albicans infection of the alimentary tract is closely related to the immune system of mice,especially in the hypofunction state of immune defense which is greater harmful to mice and at the same time,may further aggravate the deficiency state or infection,In the process of body against Candida albicans infection,a variety of immune cells and cytokines involved in immune response.
材料与方法:本实验将小鼠分层随机分成四组,即正常对照组(A组)、脾虚模型组(B组)、正常感染白念珠菌组(C组)、脾虚感染白念珠菌组(D组)。采用饮食失节加劳倦过度的复合因素制备小鼠脾虚证模型。模型成功后,经口灌给C、D组小鼠白念珠菌悬液,之后连续3周,观察各组小鼠的体重变化及一般状况的改变,记录并计算平均生存天数及存活率,并检测粪便及肾脏中的活白念珠菌的数量,测定小鼠脾指数及胸腺指数。取小鼠空肠作HE染色观察小鼠小肠黏膜形态的病理学改变,电镜观察小肠超微结构的变化。应用动物血液分析仪检测小鼠外周血中白细胞总数、中性粒细胞、淋巴细胞数及单核细胞数,并测定红细胞数及血红蛋白含量的改变;应用酶联免疫吸附法(ELISA)测定脾虚模型小鼠肠组织表达的免疫球蛋白A(IgA)、血清中白细胞介素1β(IL-1β)、腹腔巨噬细胞肿瘤坏死因子α(TNF-α)、脾细胞γ-干扰素(IFN-γ)及白细胞介素10(IL-10)的含量。应用逆转录/聚合酶链式反应(RT-PCR)方法检测肠组织局部IFN-γmRNA和IL-10mRNA的表达水平。
结果:
1.白念珠菌消化道感染对脾虚小鼠体重及一般状况的影响
脾虚小鼠比正常小鼠体重明显减轻(P＜0.01),且一般状况欠佳。正常小鼠感染后体重无明显变化,而脾虚感染组小鼠的体重下降明显(P＜0.01)。
2.白念珠菌消化道感染对脾虚小鼠生存天数及生存率的影响
脾虚小鼠平均生存天数缩短(P＜0.05),生存率下降至75%;正常小鼠感染白念珠菌后,平均生存天数无统计学意义。而脾虚小鼠感染后平均生存天数明显缩短(P＜0.01),生存率下降至55%。
3.白念珠菌消化道感染对脾虚小鼠粪便活菌数的影响
正常小鼠感染后,便活菌数呈先增高后减少的趋势,而脾虚小鼠感染后则呈逐渐增高趋势,并始终高于前者。在感染后第6天,两组小鼠的便活菌数有统计学意义(P＜0.05);感染后第9天、第12天、第15天及第18天,统计学差异显著(P＜0.01)。
4.白念珠菌消化道感染对脾虚小鼠肾脏内活菌数的影响
正常小鼠感染后,肾脏内活菌数相对较少,而脾虚小鼠感染后肾脏内活菌数明显增加(P＜0.01)。
5.白念珠菌消化道感染对脾虚小鼠脾指数及胸腺指数的影响
脾虚小鼠的脾脏及胸腺重量均低于正常小鼠,但无统计学意义。小鼠感染白念珠菌后期,脾指数及胸腺指数均明显增高,统计学差异显著(P＜0.05或P＜0.01),尤其是脾虚小鼠脾脏重量增加更为明显。
6.白念珠菌消化道感染对脾虚小鼠小肠黏膜形态学的影响
脾虚组小鼠小肠绒毛略变短,游离面上皮松散。正常小鼠感染后期,小肠绒毛变短且稀疏,游离面上皮立方形改变,固有膜空泡样改变,细胞轻度水肿。脾虚感染组小肠绒毛稀疏不完整,柱状上皮立方形改变,固有膜空泡样改变。
7.白念珠菌消化道感染对脾虚小鼠小肠黏膜超微结构的影响
正常小鼠感染后期,微绒毛较细疏且长短大小不一,胞质内线粒体稍肿胀,嵴较松散,部分呈空泡样改变。脾虚感染组小鼠小肠微绒毛短少且不整齐,线粒体肿胀,嵴断裂消失,呈空泡样改变,并可见内质网扩张、核糖体脱落等。
8.白念珠菌消化道感染对脾虚小鼠外周血细胞数量的影响
脾虚小鼠外周血中红细胞数及血红蛋白含量均有所降低,尤其是感染后期的脾虚小鼠下降更加明显(P＜0.01)。感染后小鼠体内白细胞数量增多,正常小鼠感染后期,淋巴细胞数明显增高(P＜0.01);而脾虚小鼠感染后期,单核细胞数增高明显(P＜0.01),中性粒细胞也明显增加。
9.白念珠菌消化道感染对脾虚小鼠腹腔巨噬细胞分泌TNF-α的影响
与正常组比较,脾虚组小鼠腹腔巨噬细胞TNF-α的分泌减少,而正常小鼠感染后期TNF-α的分泌增多,二者均有统计学差异(P＜0.05);脾虚感染组小鼠TNF-α的分泌则明显高于其它各组(P＜0.01)。
10.白念珠菌消化道感染对脾虚小鼠血清中IL-1β含量的影响
脾虚小鼠血清中IL-1β含量无明显改变;正常小鼠感染后期,IL-1β含量虽有增多,但无统计学意义;脾虚小鼠感染后期,IL-1β含量则明显升高(P＜0.01)。
11.白念珠菌消化道感染对脾虚小鼠小肠组织IgA含量的影响
脾虚小鼠比正常小鼠小肠组织IgA含量减少,差异显著(P＜0.01);小鼠感染后期,肠组织IgA分泌也呈下降趋势,特别是脾虚感染组小鼠IgA含量明显低于其它各组(P＜0.01)。
12.白念珠菌消化道感染对脾虚小鼠脾脏IFN-γ和IL-10表达的影响
正常小鼠感染后表达IFN-γ和IL-10的水平均高于正常组,但无统计学差异;而脾虚小鼠感染白念珠菌后期,则显著高于其它各组(P＜0.01)。
13.白念珠菌消化道感染对脾虚小鼠肠组织中IFN-γmRNA及IL-10mRNA表达的影响
与正常组比较,脾虚组小鼠IFN-γmRNA表达增高(P＜0.01),IL-10mRNA差异不明显;与脾虚组比较,正常与脾虚小鼠感染后肠组织表达IFN-γmRNA和IL-10mRNA的水平均显著升高(P＜0.01)。与正常感染白念珠菌组比较,脾虚小鼠感染后期IFN-γmRNA的表达水平仍处于高水平状态,有显著性差异(P＜0.01),但IL-10mRNA表达减少(P＜0.05)。
结论:
1.小鼠在脾虚状态下对消化道感染白念珠菌的易感性增强。可使脾虚小鼠体重显著下降,脾指数及胸腺指数明显增高,还可以使平均生存天数明显缩短,生存率大幅度下降,而且便活菌数持续增高,肾脏内活菌数也显著增加。
2.小鼠在脾虚状态下消化道感染白念珠菌后,导致小肠组织IgA含量明显减少,削弱了消化道局部免疫防御功能。更容易加重小肠黏膜形态学改变及小肠上皮细胞超微结构的病理变化。还可入血播散至其它部位,造成外周血中红细胞数量减少,血红蛋白含量降低,体内炎性细胞大量增殖。
3.消化道的白念珠菌感染是否致病与小鼠的免疫力密切相关,尤其是在免疫功能低下时危害更大,同时又进一步加重脾虚状态或感染的病情。脾虚小鼠在抗白念珠菌感染过程中,多种免疫细胞及细胞因子参与了免疫应答。
Purpose:To investigate the susceptibility of Candida albicans infection of alimentary tract in the state of deficiency of spleen and the immunological mechanisms.To illuminate the characteristics of change of susceptibility in deficiency of spleen,to further control their infection.To illuminate the relationship between immunological functions and Candida albicans and some immunological changes before and after the infection.To illuminate the immunological mechanisms of Candida albicans infection in the state of deficiency of spleen,for the prevention and treatment of the infection.
Material and method:The experimental mice were randomly divided into four groups,that is,the normal control group(A group),deficiency of spleen model group(B group),Candida albicans infection in normal group(C group),deficiency of spleen with Candida albicans infection group(D group).The animal model of spleen deficiency was prepared by using of irregular-feeding and overstrain methods.The mice in group C and D were fed with suspension of Candida albicans, in the following 3 weeks,mice in each group were observed changes in body weight and general condition.The average survival days and survival rate were recorded and calculated.The number of living Candida albicans in fecal and kidney was detected;spleen index and thymus index were also measured.The jejunum of the mice were prepared with HE staining method,and the morphological changes of jejunum were observed with optical microscope.Ultrastructural changes of small intestine were observed with electron microscopy.The total number of peripheral blood leukocytes,neutrophils,lymphocytes and mononuclear cells,and RBC number and hemoglobin content of the change were also measured with animal blood analyzer.The expression of immunoglobulin A(IgA),serum interleukin-1β (IL-1β),macrophage tumor necrosis factor-α(TNF-α),spleen cells fromγ-interferon(IFN-γ) and interleukin-10(IL-10) content in intestinal tissue of spleen deficiency mice were detected with application of enzyme-linked immunosorbent assay(ELISA).Using reverse transcription / polymerase chain reaction(RT-PCR) method detected the expression of IFN-γmRNA and IL-10mRNA level in the intestinal tissue.
Results:
1.Effects on body weight and general condition of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Body weight in spleen deficiency mice was significant lighter than normal mice(P＜0.01),with the addition of poor general condition.In normal mice after infection,no significant changes in body weight,and the weight of spleen deficiency infected mice decreased significantly(P＜0.01).
2.Effects on the survival days and survival rate of spleen deficiency mice with Candida albicans infection of the alimentary tract.
The survival days of spleen deficiency mice were reduced(P＜0.05),the survival rate dropped to 75%;the average survival days were no significant difference in normal mice infected with Candida albicans.And the average survival days was reduced significantly in spleen deficiency mice infected with Candida albicans,the survival rate also dropped to 55%.
3.Effects on the number of living fecal bacteria of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Normal mice after infection,the number of fecal living bacteria appeared a downward trend after an increase in initial stage,and that number shows an increasing trend,and always higher than the former in infected spleen deficiency mice.In the first six days after infection,the number of fecal living bacteria of the two groups mice have a statistically significance difference(P＜0.05); the first 9 days,12 days,the first 15 days and 18 days,both statistically significance difference(P＜0.01).
4.Effects on the number of living renal bacteria of spleen deficiency mice with Candida albicans infection of the alimentary tract.
In normal mice after infection,a relatively small number of living bacteria was observed in kidney,and that number have a marked increase in the kidney of infected spleen deficiency mice(P＜0.01).
5.Effects on the spleen index and thymus index of spleen deficiency mice with Candida albicans infection of the alimentary tract.
The weight of spleen and thymus in spleen deficiency mice was lower than that of normal mice,but not statistically significant.After Candida albicans infection in mice,the spleen index and thymus index were significantly higher, with statistically significant differences(P＜0.05 or P＜0.01).In particular, increased weight of spleen deficiency mice became more evident.
6.Effects on morphology of small intestinal submucosa of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Intestinal villi in spleen deficiency mice became slightly shorter,and scattered free surface epithelial.In normal mice after infection,intestinal villi became shorter and sparse,and free surface epithelial became cubic form; the inherent membrane had vacuole-like change with mild edema in cells.In infected spleen deficiency mice,small intestinal villi became sparse and incomplete,with cubic columnar epithelium changes,the inherent membrane had vacuole-like change.
7.Effects on ultrastructure of small intestinal submucosa of spleen deficiency mice with Candida albicans infection of the alimentary tract.
In normal mice after infection,microvilli became sparse and different in length and size,slightly swollen mitochondria in the cytoplasm,a looser ridge, and some showed vacuolated changes.In infected spleen deficiency mice, microvilli became untidily sparse and shorter,mitochondrial swelling, disappearance of ridge,vacuolated changes,and with addition of expansion of the endoplasmic reticulum and ribosome falling off,etc.
8.Effects on the number of peripheral blood cells of spleen deficiency mice with Candida albicans infection of the alimentary tract.
The number of peripheral blood hemoglobin content of red blood cells are reduced in spleen deficiency mice,especially in the mice after infection(P＜0.01).the number of leukocytes in infected spleen deficiency mice was significantly increased(P＜0.01);the number of mononuclear cells increased significantly(P＜0.01)in normal mice,and neutrophils also significantly increased.
9.Effects on the Secretion of TNF-αof peritoneal macrophages of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Compared to the normal group,the Secretion of TNF-αof peritoneal macrophages was reduced,and the infected normal mice was increased,both have significantly different(P＜0.05);the Secretion of infected spleen deficiency mice was significantly higher than other groups(P＜0.01).
10.Effects on the content of serum IL-1βof spleen deficiency mice with Candida albicans infection of the alimentary tract.
There was no significant change in serum IL-1βcontent in spleen deficiency mice;in final stage of infection in normal mice,serum IL-1βcontent increased, but without statistical significance,and in infected spleen deficiency mice, serum IL-1βcontent was significantly higher(P＜0.01).
11.Effects on IgA content of intestinal tissue of spleen deficiency mice with Candida albicans infection of the alimentary tract.
IgA content of intestinal tissue decreased significantly(P＜0.01)in spleen deficiency mice,compared to normal mice.After infection,intestinal IgA secretion also declined,especially in infected spleen deficiency mice,the IgA content was significantly lower than the other groups(P＜0.01).
12.Effects on the expression of IFN-γand IL-10 of spleen of spleen deficiency mice with Candida albicans infection of the alimentary tract.
The expression of IFN-γand IL-10 in normal mice after infection was higher than the normal group,but no significant difference;and the expression in infected spleen deficiency mice was significantly higher than the other groups (P＜0.01) in the final infectious stage.
13.Effects on the expression of IFN-γmRNA and IL-10mRNA of intestinal tissue of spleen deficiency mice with Candida albicans infection of the alimentary tract.
Compared to the normal group,the expression of IFN-γmRNA in spleen deficiency mice was increased(P＜0.01),and that of IL-10mRNA had no obvious difference.Compared to spleen deficiency mice,the expressions of IFN-γmRNA and IL-10mRNA were both significantly increased(P＜0.01) in the other groups. Compared to infected normal groups,the expression of IFN-γmRNA was still at a high level state in final infectious stage of infected spleen deficiency mice, but the expression of IL-10mRNA was reduced(P＜0.05).
Conclusion:
1.The susceptibility of Candida albicans of mice was enhanced in a state of spleen deficiency.Which led to a significant drop in body weight,increasing of spleen index and thymus index,the shortened average number of days,the decreased survival rate,and a sustaining increasing number of living bacteria in feces and kidney.
2.After Candida albicans infection in the alimentary tract in a state of spleen deficiency,IgA content of intestinal tissue decreased significantly,leading to hypofunction of the intestinal function of local immune defense,which caused the morphological changes of intestinal mucosa and pathological changes of intestinal epithelial cell ultrastructure.Meanwhile,bacteria could be disseminated into the blood and other parts of the body,so that cause reduction in the number of red blood cells in peripheral blood,hemoglobin decreased,the proliferation of a large number of inflammatory cells in vivo.
3.Whether pathogenic or not of Candida albicans infection of the alimentary tract is closely related to the immune system of mice,especially in the hypofunction state of immune defense which is greater harmful to mice and at the same time,may further aggravate the deficiency state or infection,In the process of body against Candida albicans infection,a variety of immune cells and cytokines involved in immune response.
引文
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