缬沙坦对阿霉素肾病肾硬化大鼠细胞凋亡及Fas和FasL表达的影响(英文)

Effects of Valsartan on Apoptosis and Expression of Fas and FasL in the Kidneys of Rats with Nephrotic Glomerulosclerosis Induced by Adriamycin

摘要:

目的：探讨血管紧张素Ⅱ1型受体拮抗剂(AT1RA)缬沙坦对阿霉素肾病肾硬化大鼠肾脏细胞凋亡及凋亡相关蛋白的影响。方法：36只SD大鼠随机分为模型组、治疗组和对照组。大鼠单侧肾切除加阿霉素注射诱导阿霉素肾病肾硬化模型。治疗组每日予缬沙坦(20 mg/kg)灌胃1次，共12周。对照组和模型组每日用等量生理盐水灌胃。采用TUNEL法检测肾脏细胞凋亡情况，计算出肾小球凋亡指数(GAI)和肾小管凋亡指数(TAI)。免疫组化法检测肾组织Fas和FasL表达。光镜下观察肾组织病理改变，并计算肾小球硬化指数(GSI)。结果：模型组较对照组肾小球硬化明显，GSI高于对照组(P<0.01)；而治谱镚SI较模型组降低，但仍高于对照组(P<0.01)。模型组和治疗组GAI和TAI较对照组显著增高(P<0.01)；而治疗组GAI和TAI均低于模型组(P<0.01)，但仍高于对照组(P<0.01)。模型组和治疗组的Fas和FasL表达较对照组亦明显增强(P<0.01)，其中治疗组低于模型组(P<0.01)。 结论：AT1RA缬沙坦可能通过降低凋亡相关蛋白Fas及FasL在肾组织表达而抑制肾脏细胞过度凋亡，从而发挥其延缓肾小球硬化的作用。

Abstract:

OBJECTIVE: To inquire into the effects of angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis correlated protein Fas and FasL in the kidneys of rats with nephrotic glomerulosclerosis induced by adriamycin. METHODS: Thirty six SD rats were randomly divided into model group, treatment group and control group. The model was established by uninephrectomy and injection of adriamycin. In the treatment group, valsartan (20 mg/kg) was delivered daily by gavage for 12 weeks. The same amount of normal saline was delivered by gavage in the control and model groups. Apoptosis was examined by means of terminal deoxynucleotidyl transferase mediated d UTP nick end labeling (TUNEL). Glomerular apoptotic index (GAI) and renal tubule apoptotic index (TAI) were calculated. Immunohistochemistry was utilized to detect the expression of Fas and FasL. The morphological changes were observed under optic microscope and the glomerulosclerosis index (GSI) was determined. RESULTS: Compared with the control group, the GSI, GAI, TAI and the expression of Fas and FasL in model and treatment groups were stronger (P< 0.01 ). Compared with model group, they decreased in treatment group (P< 0.01 ). CONCLUSIONS: Valsartan may suppress the excessive apoptosis of kidney cells by lowering the expression of Fas and FasL so as to postpone the process of glomerulosclerosis.