黄芪多糖、丹皮酚对高血压病血瘀证内皮细胞损伤模型TLR4、NF-κB表达的影响
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摘要
目的
通过TLR-NF-κB信号转导通路,探讨高血压病血瘀证的形成机理,黄芪多糖、丹皮酚治疗高血压病血瘀证的作用机制,验证高血压病血瘀证细胞模型。方法
1.对高血压病血瘀证的研究:
(1).10%的高血压病血瘀证患者血清干预人脐静脉内皮细胞(HUVEC-C)24h,建立血瘀证细胞模型(血瘀证组),非血瘀证组、健康组、空白对照组分别用同等浓度的高血压病非血瘀证患者血清、健康人血清和不含血清培养基干预相同时间。四甲基偶氮唑盐(MTT)法检测细胞的活性,倒置相差显微镜观察细胞形态。
(2).不同浓度的黄芪多糖、丹皮酚干预10%的高血压病血瘀证患者血清损伤HUVEC-C 24h,MTT法检测细胞的活性,倒置相差显微镜观察细胞形态。
(3).实时荧光定量(PCR)法测血瘀证组,非血瘀证组、健康组细胞果蝇样受体(TLR4)mRNA的表达。
(4).不同浓度的黄芪多糖、丹皮酚干预脂多糖(LPS)诱导HUVEC-C TLR4表达(24h)及核转录因子(NF-κB)活化(2h)。PCR法测TLR4 mRNA及NF-κBmRNA的表达,免疫印迹(Western-blot)技术测TLR4蛋白及NF-κB蛋白的表达。NF-κB的活化均用IκBα的降解反映。
2.对高血压病不同病情分级的研究:
(1).高血压病1级组、2级组、3级组、健康组HUVEC-C分别用10%的高血压病1级患者血清、2级患者血清、3级患者血清、健康人血清干预24h,MTT法检测细胞的活性,倒置相差显微镜观察细胞形态。
(2).PCR法检测高血压病1级组、2级组、3级组、健康组细胞TLR4 mRNA的表达。
结果
1.血清作用24h后,细胞活性按健康组(0.3697±0.0548)、非血瘀证组(0.3196±0.0479)、血瘀证组(0.2120±0.0317)、空白组(0.1853±0.0129)的顺序降低,组间差异显著(P<0.01或P<0.001);血瘀证组细胞逐渐收缩变形,细胞间隙增大,胞浆内有暗色颗粒。
2.黄芪多糖、丹皮酚可减轻高血压病血瘀证患者血清对细胞形态变化的影响;细胞活性呈剂量依赖性增强,APS各组的OD值为:健康组(0.4419+±0.0216)、血瘀证组(0.2243±0.0298)、小剂量组(0.2340±0.0376)、中剂量组(0.2656±0.0233)、大剂量组(0.3487±0.0469),组间比较差异显著(P<0.01或P<0.001);Pae各组的OD值为:健康组(0.5290±0.0946)、血瘀证组(0.2888±0.0319)、小剂量组(0.3227±0.0371)、中剂量组(0.3732±0.0736)、大剂量组(0.4510±0.0909),组间差异显著(P<0.01或P<0.001)。
3.血清作用24h后,TLR4 mRNA的表达按健康组(5.4160×10~(-4)±0.2488×10~(-4))、非血瘀证组(6.4692×10~(-4)±0.0956×10~(-4))、血瘀证组(8.2598×10~(-4)±0.2685×10~(-4))的顺序逐渐增高,组间差异显著(P<0.01)。
4.黄芪多糖、丹皮酚可呈剂量依赖性减少LPS诱导的TLR4 mRNA高表达,各组值分别为,健康组(5.4160×10~(-4)±0.2488×10~(-4))、血瘀证组(8.2598×10~(-4)±0.2685×10~(-4))、LPS诱导组(97.3569×10~(-4)±0.9599×10~(-4))、APS小剂量组(33.4288×10~(-4)±0.8112×10~(-4))、APS中剂量组(13.5707×10~(-4)±0.6434×10~(-4))、APS大剂量组(7.2484×10~(-4)±0.0566×10~(-4))、Pae小剂量组(10.7065×10~(-4)±0.6657×10~(-4))、Pae中剂量组(7.1994×10~(-4)±0.0939×10~(-4))、Pae大剂量组(6.4403×10~(-4)±0.1271×10~(-4));黄芪多糖、丹皮酚可呈剂量依赖性抑制LPS诱导的IκBαmRNA的降解,各组值分别为,健康组(0.4536±0.0164)、LPS诱导组(0.0665±0.0007)、APS小剂量组(0.0873±0.0007)、APS中剂量组(0.1333±0.0005)、APS大剂量组(0.1371±0.0004)、Pae小剂量组(0.0973±0.0003)、Pae中剂量组(O.1357±0.0016)、Pae大剂量组(0.1425±0.0012)。
5.黄芪多糖、丹皮酚可抑制LPS诱导的TLR4蛋白高表达和IκBα蛋白的降解。
6.血清作用24h后,细胞活性按健康组(0.4609±0.0382)、高血压病1级组(0.4241±0.0270)、2级组(0.3330±0.0249)、3级组(0.2116±0.0222)的顺序降低,健康组高于高血压病1级组,但差异不显著(P>0.05),与其它各组差异显著(P<0.01);2级组、3级组细胞逐渐收缩变形,细胞间隙增大,胞浆内有暗色颗粒。
7.血清作用24h后,TLR4 mRNA的表达按健康组(5.4160×10~(-4)±0.2488×10~(-4))、高血压病2级组(5.9333×10~(-4)±0.3431×10~(-4))、1级组(8.0697×10~(-4)±0.1249×10~(-4))、3级组(8.1314×10~(-4)±0.0702×10~(-4))的顺序逐渐增加,健康组低于1级组和3级组,差异显著(P<0.01);健康组低于2级组,但差异不显著(P>0.05)。
结论
1.血瘀证内皮细胞损伤模型符合中医发病因素,体现“病”“证”结合特点,又易于复制,有较高的可重复性。
2.APS、Pae可减轻高血压病患者血清对内皮细胞的损伤,增强细胞活性和维持细胞形态结构。
3.TLR-NF-κB信号途径介导的炎症反应和免疫紊乱可能是高血压病血瘀证形成的机制之一。
4.APS、Pae通过降低TLR4表达,抑制IκBα降解起抗炎调节免疫的作用,这可能是其活血化瘀作用的机理之一。
5.APS、Pae可通过降低TLR4的表达,抑制IκBα的降解,抗炎、调节免疫,起保护内皮细胞的作用。
6.TLR-NF-κB信号途径介导了高血压病的炎症反应和免疫紊乱,这可能是高血压病的发病机制之一。
Objective
The research was observe the TLR-NF-kB signal pathway, to investigate the influencing mechanisms in the development of blood stasis syndrome(BSS) associated with hypertension disease, probe the pharmacological mechanism of APS and Pae treatment BSS associated with hypertension disease, confirmation vascular endothelial cells(VECs) injury model of BSS associated with hypertension disease.
Methods
1. Research of BSS associated with hypertension disease:
(1).The human umbilical vein endothelial cells (HUVEC-Cs) were intervened by the 10% serum of the patient of BSS associated with hypertension disease for 24h to establish VECs injury model of BSS associated with hypertension disease(the blood stasis syndrome control group), the non-blood stasis syndrome control group、the normal control group and the blank control group were intervened by the 10% serum of the patient of non-blood stasis syndrome (NBSS) associated with hypertension disease、the 10% serum of the healthy human and non-serum medium separately. The activeness of the HUVEC-Cs was determined by MTT assay and the change of cells was observed by the inverse phase contrast microscope.
(2).The HUVEC-Cs were effected by the 10% serum of the patient of BSS associated with hypertension disease and different dosage APS or Pae during the same time for 24h. The activeness of the HUVEC-Cs was determined by MTT assay and the change of cells was observed by the inverse phase contrast microscope.
(3).The TLR4mRNA expression in HUVEC-Cs of the blood stasis syndrome control group、the non-blood stasis syndrome control group and the normal control group was detected by real time PCR.
(4).The level of TLR4 expression(24h) and NF-kB activation(2h) in lipopolysaccharide(LPS) activated HUVEC-Cs were effected by different dosage APS or Pae during the same time. TLR4 mRNA and NF-kB mRNA were detected by real time PCR, TLR4 protein and NF-kB protein were detected by western blot. The NF-kB expression reflected with IkBα.
2. Research of hypertension disease with different graduation:
(1).The HUVEC-Cs of the normal control group、the grade 1 essential hypertension control group、the grade 2 essential hypertension control group、the grade 3 essential hypertension control group were intervened by the 10% serum of the healthy human、the patient of grade 1 essential hypertension disease、the patient of grade 2 essential hypertension disease、the patient of grade 3 essential hypertension disease separately for 24h. The activeness of the HUVEC-Cs was determined by MTT assay and the change of cells was observed by the inverse phase contrast microscope.
(2).The TLR4 expression level in the HUVEC-Cs of the normal control group、the grade 1 essential hypertension control group、the grade 2 essential hypertension control group、the grade 3 essential hypertension control group was detected by real time PCR,
Results
1. After the serum acted on the HUVEC-Cs for 24h, the HUVEC-Cs activeness was reduced according to the order of the normal control group(0.3697±0.0548)、the non-blood stasis syndrome control group(0.3196±0.0479)、the blood stasis syndrome control group(0.2120±0.0317)、the blank control group (0.1853±0.0129), there was a significant difference (P＜0.01 or P＜0.001); the HUVEC-Cs of the blood stasis syndrome control group shrank, the intercellular space increased, dark granules existed in the cytoplasm.
2. APS and Pae had the protective function of lighten the HUVEC-Cs Shape change effected by the serum the patient of BSS associated with hypertension disease; The activeness of the HUVEC-Cs was increased on dose-dependent rule, The OD of each APS groups was: the normal control group(0.4419±0.0216)、the blood stasis syndrome control group(0.2243±0.0298)、the APS low dose group(0.2340±0.0376)、the APS middle dose group(0.2656±0.0233)、the APS high dose group(0.3487±0.0469), the difference is distinct(P<0.01 or P<0.001); he OD of each Pae groups was: the normal control group(0.5290±0.0946)、the blood stasis syndrome control group(0.2888±0.0319)、the Pae low dose group(0.3227±0.0371)、the Pae middle dose group(0.3732±0.0736)、the Pae high dose group(0.4510±0.0909), the difference is distinct(P<0.01 or P<0.001)。
3. After the serum acted on the HUVEC-Cs for 24h, the HUVEC-Cs TLR4mRNA expression was increased according to the order of the normal control group(5.4160×10~(-4)±0.2488×10~(-4))、the non-blood stasis syndrome control group(6.4692×10~(-4)±0.0956×10~(-4))、the blood stasis syndrome control group(8.2598×10~(-4)±0.2685×10~(-4)), there was a significant difference(P<0.01).
4. APS and Pae had the function of reduce the TLR4mRNA expression in LPS activated HUVEC-Cs on dose-dependent rule, The TLR4mRNA expression level of each groups was: the normal control group(5.4160×10~(-4)±0.2488×10~(-4))、the blood stasis syndrome control group (8.2598×10~(-4)±0.2685×10~(-4))、the LPS control group (97.3569×10~(-4)±0.9599×10~(-4))，the APS low dose group(33.4288×10~(-4)±0.8112×10~(-4))、the APS middle dose group(13.5707×10~(-4)±0.6434×10~(-4))、the APS high dose group(7.2484×10~(-4)±0.0566×10~(-4))、the Pae low dose group(10.7065×10~(-4)±0.6657×10~(-4))、the Pae middle dose group(7.1994×10~(-4)±0.0939×10~(-4))、the Pae high dose group(6.4403×10~(-4)±0.1271×10~(-4)).APS and Pae had the function of suppress the IκBmRNA degeneration in LPS activated HUVEC-Cs on dose-dependent, The NF-κBmRNA expression level of each groups was: the normal control group(0.4536±0.0164)、the LPS control group (0.0665±0.0007),the APS low dose group(0.0873±0.0007)、the APS middle dose group(0.1333±0.0005)、the APS high dose group(0.1371±0.0004)、the Pae low dose group(0.0973±0.0003)、the Pae middle dose group(0.1357±0.0016)、the Pae high dose group(0.1425±0.0012).
5. APS and Pae had the function of reduce the TLR4 protein expression and suppress the IκB protein degeneration in LPS activated HUVEC-Cs.
6. After the serum acted on the HUVEC-Cs for 24h, the HUVEC-Cs activeness was reduced according to the order of the normal control group(0.4609±0.0382)、the grade 1 essential hypertension control group (0.4241±0.0270)、the grade 2 essential hypertension control group(0.3330±0.0249)、the grade 3 essential hypertension control group(0.2116±0.0222).There was a significant difference(P＜0.01) between the normal control group and the grade 2 essential hypertension control group、the grade 3 essential hypertension control group, but no significant difference（P > 0.05)between the normal control group and the grade 1 essential hypertension control group. The HUVEC-Cs of the grade 2 essential hypertension control group and the grade 3 essential hypertension control group shrank, the intercellular space increased, dark granules existed in the cytoplasm.
7. After the serum acted on the HUVEC-Cs for 24h, the HUVEC-Cs TLR4mRNA expression was increased according to the order of the normal control group(5.4160×10~(-4)±0.2488×10~(-4))、the grade 2 essential hypertension control group (5.9333×10~(-4)±0.3431×10~(-4))、the grade 1 essential hypertension control group(8.0697×10~(-4)±0.1249×10~(-4))、the grade 3 essential hypertension control group (8.1314×10~(-4)±0.0702×10~(-4)).There was a significant difference(P<0.01) between the normal control group and the grade 1 essential hypertension control group、the grade 3 essential hypertension control group, but no significant difference(P > 0.05) between the normal control group and the grade 2 essential hypertension control group.
Conclusions
1. The VEC injury model of BSS associated with hypertension disease conforms to the morbidity factor of Traditional Chinese Medicine, explain the characteristic of "disease" and "syndrome" unify, and easy to duplicate, has the high rePaetability.
2. APS and Pae can lighten the injury of the HUVEC-Cs that effected by the serum the patient of BSS associated with hypertension disease, increase cells activeness and maintenance the shape of the cells.
3. Inflammatory reaction and immunity disorder initiated by TLR-NF-kB signal pathway is one of the influencing mechanisms in the development of blood stasis syndrome(BSS) associated with hypertension disease.
4. APS and Pae can sterilization and adjustment immunity by reduce the TLR4 expression and suppress the IκBαdegeneration, it is possibly one of the pharmacological mechanism of APS and Pae with activating blood function.
5. APS and Pae exert the protection function to HUVEC-Cs, sterilization and adjustment immunity by reduce the TLR4 expression and suppress the IkBαdegeneration.
6. The TLR-NF-kB signal pathway initiates essential hypertension inflammatory reaction and immunity disorder, it possibly one of the influencing mechanisms of essential hypertension morbidity.
通过TLR-NF-κB信号转导通路,探讨高血压病血瘀证的形成机理,黄芪多糖、丹皮酚治疗高血压病血瘀证的作用机制,验证高血压病血瘀证细胞模型。方法
1.对高血压病血瘀证的研究:
(1).10%的高血压病血瘀证患者血清干预人脐静脉内皮细胞(HUVEC-C)24h,建立血瘀证细胞模型(血瘀证组),非血瘀证组、健康组、空白对照组分别用同等浓度的高血压病非血瘀证患者血清、健康人血清和不含血清培养基干预相同时间。四甲基偶氮唑盐(MTT)法检测细胞的活性,倒置相差显微镜观察细胞形态。
(2).不同浓度的黄芪多糖、丹皮酚干预10%的高血压病血瘀证患者血清损伤HUVEC-C 24h,MTT法检测细胞的活性,倒置相差显微镜观察细胞形态。
(3).实时荧光定量(PCR)法测血瘀证组,非血瘀证组、健康组细胞果蝇样受体(TLR4)mRNA的表达。
(4).不同浓度的黄芪多糖、丹皮酚干预脂多糖(LPS)诱导HUVEC-C TLR4表达(24h)及核转录因子(NF-κB)活化(2h)。PCR法测TLR4 mRNA及NF-κBmRNA的表达,免疫印迹(Western-blot)技术测TLR4蛋白及NF-κB蛋白的表达。NF-κB的活化均用IκBα的降解反映。
2.对高血压病不同病情分级的研究:
(1).高血压病1级组、2级组、3级组、健康组HUVEC-C分别用10%的高血压病1级患者血清、2级患者血清、3级患者血清、健康人血清干预24h,MTT法检测细胞的活性,倒置相差显微镜观察细胞形态。
(2).PCR法检测高血压病1级组、2级组、3级组、健康组细胞TLR4 mRNA的表达。
结果
1.血清作用24h后,细胞活性按健康组(0.3697±0.0548)、非血瘀证组(0.3196±0.0479)、血瘀证组(0.2120±0.0317)、空白组(0.1853±0.0129)的顺序降低,组间差异显著(P<0.01或P<0.001);血瘀证组细胞逐渐收缩变形,细胞间隙增大,胞浆内有暗色颗粒。
2.黄芪多糖、丹皮酚可减轻高血压病血瘀证患者血清对细胞形态变化的影响;细胞活性呈剂量依赖性增强,APS各组的OD值为:健康组(0.4419+±0.0216)、血瘀证组(0.2243±0.0298)、小剂量组(0.2340±0.0376)、中剂量组(0.2656±0.0233)、大剂量组(0.3487±0.0469),组间比较差异显著(P<0.01或P<0.001);Pae各组的OD值为:健康组(0.5290±0.0946)、血瘀证组(0.2888±0.0319)、小剂量组(0.3227±0.0371)、中剂量组(0.3732±0.0736)、大剂量组(0.4510±0.0909),组间差异显著(P<0.01或P<0.001)。
3.血清作用24h后,TLR4 mRNA的表达按健康组(5.4160×10~(-4)±0.2488×10~(-4))、非血瘀证组(6.4692×10~(-4)±0.0956×10~(-4))、血瘀证组(8.2598×10~(-4)±0.2685×10~(-4))的顺序逐渐增高,组间差异显著(P<0.01)。
4.黄芪多糖、丹皮酚可呈剂量依赖性减少LPS诱导的TLR4 mRNA高表达,各组值分别为,健康组(5.4160×10~(-4)±0.2488×10~(-4))、血瘀证组(8.2598×10~(-4)±0.2685×10~(-4))、LPS诱导组(97.3569×10~(-4)±0.9599×10~(-4))、APS小剂量组(33.4288×10~(-4)±0.8112×10~(-4))、APS中剂量组(13.5707×10~(-4)±0.6434×10~(-4))、APS大剂量组(7.2484×10~(-4)±0.0566×10~(-4))、Pae小剂量组(10.7065×10~(-4)±0.6657×10~(-4))、Pae中剂量组(7.1994×10~(-4)±0.0939×10~(-4))、Pae大剂量组(6.4403×10~(-4)±0.1271×10~(-4));黄芪多糖、丹皮酚可呈剂量依赖性抑制LPS诱导的IκBαmRNA的降解,各组值分别为,健康组(0.4536±0.0164)、LPS诱导组(0.0665±0.0007)、APS小剂量组(0.0873±0.0007)、APS中剂量组(0.1333±0.0005)、APS大剂量组(0.1371±0.0004)、Pae小剂量组(0.0973±0.0003)、Pae中剂量组(O.1357±0.0016)、Pae大剂量组(0.1425±0.0012)。
5.黄芪多糖、丹皮酚可抑制LPS诱导的TLR4蛋白高表达和IκBα蛋白的降解。
6.血清作用24h后,细胞活性按健康组(0.4609±0.0382)、高血压病1级组(0.4241±0.0270)、2级组(0.3330±0.0249)、3级组(0.2116±0.0222)的顺序降低,健康组高于高血压病1级组,但差异不显著(P>0.05),与其它各组差异显著(P<0.01);2级组、3级组细胞逐渐收缩变形,细胞间隙增大,胞浆内有暗色颗粒。
7.血清作用24h后,TLR4 mRNA的表达按健康组(5.4160×10~(-4)±0.2488×10~(-4))、高血压病2级组(5.9333×10~(-4)±0.3431×10~(-4))、1级组(8.0697×10~(-4)±0.1249×10~(-4))、3级组(8.1314×10~(-4)±0.0702×10~(-4))的顺序逐渐增加,健康组低于1级组和3级组,差异显著(P<0.01);健康组低于2级组,但差异不显著(P>0.05)。
结论
1.血瘀证内皮细胞损伤模型符合中医发病因素,体现“病”“证”结合特点,又易于复制,有较高的可重复性。
2.APS、Pae可减轻高血压病患者血清对内皮细胞的损伤,增强细胞活性和维持细胞形态结构。
3.TLR-NF-κB信号途径介导的炎症反应和免疫紊乱可能是高血压病血瘀证形成的机制之一。
4.APS、Pae通过降低TLR4表达,抑制IκBα降解起抗炎调节免疫的作用,这可能是其活血化瘀作用的机理之一。
5.APS、Pae可通过降低TLR4的表达,抑制IκBα的降解,抗炎、调节免疫,起保护内皮细胞的作用。
6.TLR-NF-κB信号途径介导了高血压病的炎症反应和免疫紊乱,这可能是高血压病的发病机制之一。
Objective
The research was observe the TLR-NF-kB signal pathway, to investigate the influencing mechanisms in the development of blood stasis syndrome(BSS) associated with hypertension disease, probe the pharmacological mechanism of APS and Pae treatment BSS associated with hypertension disease, confirmation vascular endothelial cells(VECs) injury model of BSS associated with hypertension disease.
Methods
1. Research of BSS associated with hypertension disease:
(1).The human umbilical vein endothelial cells (HUVEC-Cs) were intervened by the 10% serum of the patient of BSS associated with hypertension disease for 24h to establish VECs injury model of BSS associated with hypertension disease(the blood stasis syndrome control group), the non-blood stasis syndrome control group、the normal control group and the blank control group were intervened by the 10% serum of the patient of non-blood stasis syndrome (NBSS) associated with hypertension disease、the 10% serum of the healthy human and non-serum medium separately. The activeness of the HUVEC-Cs was determined by MTT assay and the change of cells was observed by the inverse phase contrast microscope.
(2).The HUVEC-Cs were effected by the 10% serum of the patient of BSS associated with hypertension disease and different dosage APS or Pae during the same time for 24h. The activeness of the HUVEC-Cs was determined by MTT assay and the change of cells was observed by the inverse phase contrast microscope.
(3).The TLR4mRNA expression in HUVEC-Cs of the blood stasis syndrome control group、the non-blood stasis syndrome control group and the normal control group was detected by real time PCR.
(4).The level of TLR4 expression(24h) and NF-kB activation(2h) in lipopolysaccharide(LPS) activated HUVEC-Cs were effected by different dosage APS or Pae during the same time. TLR4 mRNA and NF-kB mRNA were detected by real time PCR, TLR4 protein and NF-kB protein were detected by western blot. The NF-kB expression reflected with IkBα.
2. Research of hypertension disease with different graduation:
(1).The HUVEC-Cs of the normal control group、the grade 1 essential hypertension control group、the grade 2 essential hypertension control group、the grade 3 essential hypertension control group were intervened by the 10% serum of the healthy human、the patient of grade 1 essential hypertension disease、the patient of grade 2 essential hypertension disease、the patient of grade 3 essential hypertension disease separately for 24h. The activeness of the HUVEC-Cs was determined by MTT assay and the change of cells was observed by the inverse phase contrast microscope.
(2).The TLR4 expression level in the HUVEC-Cs of the normal control group、the grade 1 essential hypertension control group、the grade 2 essential hypertension control group、the grade 3 essential hypertension control group was detected by real time PCR,
Results
1. After the serum acted on the HUVEC-Cs for 24h, the HUVEC-Cs activeness was reduced according to the order of the normal control group(0.3697±0.0548)、the non-blood stasis syndrome control group(0.3196±0.0479)、the blood stasis syndrome control group(0.2120±0.0317)、the blank control group (0.1853±0.0129), there was a significant difference (P＜0.01 or P＜0.001); the HUVEC-Cs of the blood stasis syndrome control group shrank, the intercellular space increased, dark granules existed in the cytoplasm.
2. APS and Pae had the protective function of lighten the HUVEC-Cs Shape change effected by the serum the patient of BSS associated with hypertension disease; The activeness of the HUVEC-Cs was increased on dose-dependent rule, The OD of each APS groups was: the normal control group(0.4419±0.0216)、the blood stasis syndrome control group(0.2243±0.0298)、the APS low dose group(0.2340±0.0376)、the APS middle dose group(0.2656±0.0233)、the APS high dose group(0.3487±0.0469), the difference is distinct(P<0.01 or P<0.001); he OD of each Pae groups was: the normal control group(0.5290±0.0946)、the blood stasis syndrome control group(0.2888±0.0319)、the Pae low dose group(0.3227±0.0371)、the Pae middle dose group(0.3732±0.0736)、the Pae high dose group(0.4510±0.0909), the difference is distinct(P<0.01 or P<0.001)。
3. After the serum acted on the HUVEC-Cs for 24h, the HUVEC-Cs TLR4mRNA expression was increased according to the order of the normal control group(5.4160×10~(-4)±0.2488×10~(-4))、the non-blood stasis syndrome control group(6.4692×10~(-4)±0.0956×10~(-4))、the blood stasis syndrome control group(8.2598×10~(-4)±0.2685×10~(-4)), there was a significant difference(P<0.01).
4. APS and Pae had the function of reduce the TLR4mRNA expression in LPS activated HUVEC-Cs on dose-dependent rule, The TLR4mRNA expression level of each groups was: the normal control group(5.4160×10~(-4)±0.2488×10~(-4))、the blood stasis syndrome control group (8.2598×10~(-4)±0.2685×10~(-4))、the LPS control group (97.3569×10~(-4)±0.9599×10~(-4))，the APS low dose group(33.4288×10~(-4)±0.8112×10~(-4))、the APS middle dose group(13.5707×10~(-4)±0.6434×10~(-4))、the APS high dose group(7.2484×10~(-4)±0.0566×10~(-4))、the Pae low dose group(10.7065×10~(-4)±0.6657×10~(-4))、the Pae middle dose group(7.1994×10~(-4)±0.0939×10~(-4))、the Pae high dose group(6.4403×10~(-4)±0.1271×10~(-4)).APS and Pae had the function of suppress the IκBmRNA degeneration in LPS activated HUVEC-Cs on dose-dependent, The NF-κBmRNA expression level of each groups was: the normal control group(0.4536±0.0164)、the LPS control group (0.0665±0.0007),the APS low dose group(0.0873±0.0007)、the APS middle dose group(0.1333±0.0005)、the APS high dose group(0.1371±0.0004)、the Pae low dose group(0.0973±0.0003)、the Pae middle dose group(0.1357±0.0016)、the Pae high dose group(0.1425±0.0012).
5. APS and Pae had the function of reduce the TLR4 protein expression and suppress the IκB protein degeneration in LPS activated HUVEC-Cs.
6. After the serum acted on the HUVEC-Cs for 24h, the HUVEC-Cs activeness was reduced according to the order of the normal control group(0.4609±0.0382)、the grade 1 essential hypertension control group (0.4241±0.0270)、the grade 2 essential hypertension control group(0.3330±0.0249)、the grade 3 essential hypertension control group(0.2116±0.0222).There was a significant difference(P＜0.01) between the normal control group and the grade 2 essential hypertension control group、the grade 3 essential hypertension control group, but no significant difference（P > 0.05)between the normal control group and the grade 1 essential hypertension control group. The HUVEC-Cs of the grade 2 essential hypertension control group and the grade 3 essential hypertension control group shrank, the intercellular space increased, dark granules existed in the cytoplasm.
7. After the serum acted on the HUVEC-Cs for 24h, the HUVEC-Cs TLR4mRNA expression was increased according to the order of the normal control group(5.4160×10~(-4)±0.2488×10~(-4))、the grade 2 essential hypertension control group (5.9333×10~(-4)±0.3431×10~(-4))、the grade 1 essential hypertension control group(8.0697×10~(-4)±0.1249×10~(-4))、the grade 3 essential hypertension control group (8.1314×10~(-4)±0.0702×10~(-4)).There was a significant difference(P<0.01) between the normal control group and the grade 1 essential hypertension control group、the grade 3 essential hypertension control group, but no significant difference(P > 0.05) between the normal control group and the grade 2 essential hypertension control group.
Conclusions
1. The VEC injury model of BSS associated with hypertension disease conforms to the morbidity factor of Traditional Chinese Medicine, explain the characteristic of "disease" and "syndrome" unify, and easy to duplicate, has the high rePaetability.
2. APS and Pae can lighten the injury of the HUVEC-Cs that effected by the serum the patient of BSS associated with hypertension disease, increase cells activeness and maintenance the shape of the cells.
3. Inflammatory reaction and immunity disorder initiated by TLR-NF-kB signal pathway is one of the influencing mechanisms in the development of blood stasis syndrome(BSS) associated with hypertension disease.
4. APS and Pae can sterilization and adjustment immunity by reduce the TLR4 expression and suppress the IκBαdegeneration, it is possibly one of the pharmacological mechanism of APS and Pae with activating blood function.
5. APS and Pae exert the protection function to HUVEC-Cs, sterilization and adjustment immunity by reduce the TLR4 expression and suppress the IkBαdegeneration.
6. The TLR-NF-kB signal pathway initiates essential hypertension inflammatory reaction and immunity disorder, it possibly one of the influencing mechanisms of essential hypertension morbidity.
引文
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