摘要
目的研究白芍总苷(total glucosides of paeony,TGP)对庆大霉素(gentamicin,GM)所致大鼠急性肾功能衰竭(acute renal failure,ARF)的保护作用并初探其可能的作用机制。方法 120只实验用Wistar大鼠通过腹腔注射GM制备ARF大鼠模型,随机分为模型对照组、肾炎康复片800 mg/(kg·d)组、TGP低[75mg/(kg·d)]、中[150 mg/(kg·d)]、高[300 mg/(kg·d)]剂量组,各20只;并取20只同龄Wistar大鼠设为正常对照组;各组均连续14 d给药(1次/d),正常对照组同步给予生理盐水。收集并测量24 h尿量,测定24 h尿蛋白量(Pro)和N-乙酰-β-氨基葡萄糖苷酶(NAG酶)活性;测定肾功能相关指标;计算肾脏指数,HE染色法观察肾脏组织病变并进行损伤评分、电子显微镜观察肾脏组织细胞超微结构变化,测定肾脏组织氧化应激监测指标,酶联免疫吸附法(ELISA)检测肾脏组织巨噬细胞炎症蛋白-2(MIP-2)、单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)含量。结果与模型对照组比较,TGP中、高剂量组GM所致ARF大鼠24 h尿量和Pro减少、尿NAG酶活性降低(P<0.05或P<0.01);肾功能指标明显改善(血清BUN、SCr含量均显著降低,P<0.05或P<0.01),肾脏质量显著降低、肾脏指数显著减小(P<0.05或P<0.01),肾脏组织结构病变及细胞超微结构改变均明显改善,损伤评分显著降低(P<0.05或P<0.01),SOD、CAT活性升高且MDA含量降低(P<0.05或P<0.01),MIP-2、MCP-1、TNF-α含量降低(P<0.05或P<0.01)。结论TGP对GM所致ARF大鼠肾组织损伤具有一定的保护作用,作用机制可能与其改善肾功能、抗氧化、抑制炎症有关。
Objective To investigate the protective effect of total glucosides of paeony(TGP) on acute renal failure(ARF) induced by gentamicin(GM) and its possible mechanism.Methods One hundred experimental Wistar rats were used to made ARF rat model by intraperitoneal injection of GM.The rat models were randomly divided into model control group,Nephritisehabilitation tablets group(800 mg/(kg·d)),TGP low-dose group(75 mg/(kg·d)),TGPmedium-dose group(150 mg/(kg·d)),TGP high-dosegroup(300 mg/(kg·d)),20 rats in each group.Twenty Wistar rats of the same age were selected as normal control group.Each group was given saline for 14 d(once a day),and the normal control group was given saline at the same time.24 h urine volume was collected and measured,24 h urinary protein content(Pro) and NAG activity were measured,renal function related indicators were measured,renal index was calculated,renal pathological changes were observed.HE staining was used to observe the pathological changes of kidney tissues,and to evaluate injury score.Ultrastructural changes of renal tissue cells were observed by electron microscopy,oxidative stress monitoring indicators were determined,and the contents of MIP-2,MCP-1 and TNF-αwere detected by ELISA.Results Compared with model control group,the 24 h urine volume,Pro and NAG activity of ARF rats induced by GM in TGP medium-dose and high-dose groups significantly decreased and the activity of NAG were significantly decreased(P<0.05,P<0.01).The renal function indicators significant improved(thecontent of BUN,SCr significantly decreased(P<0.05,P<0.01).The quality of kidney significantly decreased,the index of kidney significantly decreased(P<0.05,P<0.01).The pathological changes of renal tissue and ultrastructure significantly improved,the injury scores significantly decreased(P<0.05,P<0.01).The activities of SOD and CAT increased and the content of MDA decreased(P<0.05,P<0.01),while the contents of MIP-2,MCP-1 and TNF-a decreased(P<0.05,P<0.01).renal weight,renal index were significantly decreased(P<0.05,P<0.01).Both of renal tissue structure lesions and cell ultrastructural changes were significantly improved,the damage score were significantly reduced(P<0.05 or P<0.01); the activity of SOD,CAT in renal tissue were significantly increased and the level of MDA were decreased(P<0.05 or P<0.01); the content of MIP-2,MCP-1,TNF-α were significantly decreased(P<0.05 or P<0.01).Conclusion TGP has a protective effect on renal tissue injury induced by GM in ARF rats.Its mechanism may be related to its improvement of renal function,antioxidation and inhibition of inflammation.
引文
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