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目的 探讨血管紧张素Ⅱ 1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 (2 0mg/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 .0 1) ;而治疗组GSI较模型组降低 ,但仍高于对照组 (P <0 .0 1)。模型组和治疗组GAI和TAI较对照组显著增高 (P <0 .0 1) ;而治疗组GAI和TAI均低于模型组(P <0 .0 1) ,但仍高于对照组 (P <0 .0 1)。模型组和治疗组的Fas和FasL表达较对照组亦明显增强 (P <0 .0 1) ,其中治疗组低于模型组 (P <0 .0 1)。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。
Objective To investigate the effects of valsartan, an angiotensin Ⅱ type 1 receptor antagonist (AT1RA), on apoptosis and apoptosis-related proteins in kidney of adriamycin nephrosis rats. Methods Thirty - six SD rats were randomly divided into model group, treatment group and control group. Induction of doxorubicin nephropathy in rats by unilateral nephrectomy plus doxorubicin injection. The treatment group daily valsartan (20mg / kg) gavage 1 times for 12 weeks. The control group and model group were orally administered with the same amount of normal saline daily. Apoptosis of renal cells was detected by TUNEL method. Glomerular apoptosis index (GAI) and tubular apoptosis index (TAI) were calculated. Immunohistochemistry was used to detect the expression of Fas and FasL in renal tissue. The pathological changes of renal tissue were observed under light microscope and the glomerulosclerosis index (GSI) was calculated. Results Compared with the control group, glomerulosclerosis was obvious in model group and GSI was higher than that in control group (P <0.01). The GSI in treatment group was lower than that in model group, but still higher than that in control group (P <0.01). GAI and TAI in model group and treatment group were significantly higher than those in control group (P <0.01), while GAI and TAI in treatment group were lower than those in model group (P <0.01), but still higher than those in control group <0 .0 1). The expressions of Fas and FasL in model group and treatment group were significantly higher than those in control group (P <0.01). The treatment group was lower than model group (P <0.01). Conclusion AT1RA valsartan may inhibit the excessive apoptosis of renal cells by decreasing the expressions of Fas and FasL in kidney and thus play a role in delaying the progression of glomerulosclerosis.