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目的:观察红花黄色素注射液对膜性肾病(MN)大鼠模型血液生化指标及对肾组织基质金属蛋白酶抑制物-1(TIMP-1)、基质金属蛋白酶-9(MMP-9)表达的影响,探讨红花黄色素注射液对MN大鼠的肾保护作用和可能机制。方法:将60只SD大鼠随机选取10只为正常对照组,其余50只进行造模,造模成功后将大鼠随机分为模型对照组、贝那普利组、红花黄色素注射液(6.5mg/kg、13mg/kg、26mg/kg)组,每组各10只,各组按相应剂量给药,在给药的第4周末检测大鼠24小时尿蛋白定量(UTP)、血清总胆固醇(TC)、甘油三酯(TG)、总蛋白(TP)、白蛋白(ALB)、尿素氮(BUN)、肌酐(Scr)水平;采用电镜、免疫荧光观察肾脏病理形态学变化,原位杂交技术检测各组大鼠肾组织TIMP-1、MMP-9的表达情况。结果:治疗结束后,与模型对照组比较,各治疗组UTP、TC、TG均明显降低,各治疗组TP、ALB均明显升高。红花黄色素注射液(6.5mg/kg、13mg/kg、26mg/kg)组与贝那普利组UTP、TC、TG、TP、ALB比较差距无统计学意义。与正常对照组比较,各治疗组及模型对照组BUN、Scr均未见明显变化,差异无统计学意义。治疗结束后,与模型对照组比较,各治疗组TIMP-1 mRNA表达显著下调,MMP-9mRNA表达显著上调(P<0.05);各治疗组间TIMP-1、MMP-9mRNA比较差距无统计学意义。结论:红花黄色素注射液对MN大鼠的肾保护作用可能与其能够下调TIMP-1、上调MMP-9的表达有关。
OBJECTIVE: To observe the effects of safflor yellow injection on the blood biochemical parameters and the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9) in the rat model of membranous nephropathy To investigate the renal protective effect of safflor yellow injection on MN rats and its possible mechanism. Methods: Sixty Sprague-Dawley rats were randomly selected as the normal control group and the remaining 50 were used for modeling. After successful modeling, the rats were randomly divided into model control group, benazepril group, safflower yellow injection (6.5mg / kg, 13mg / kg, 26mg / kg), 10 rats in each group. The rats in each group were given the corresponding doses. Urine proteinuria (UTP) (TC), triglyceride (TG), total protein (TP), albumin (ALB), urea nitrogen (BUN) and creatinine (Scr) were measured. The pathological changes of kidney were observed by electron microscope and immunofluorescence. Bit hybridization technique was used to detect the expression of TIMP-1 and MMP-9 in the kidney of each group. Results: Compared with the model control group, the levels of UTP, TC and TG in each treatment group were significantly decreased after treatment, and the levels of TP and ALB in each treatment group were significantly increased. The differences of UTP, TC, TG, TP and ALB between safflower yellow injection (6.5mg / kg, 13mg / kg, 26mg / kg) and benazepril group were not statistically significant. Compared with the normal control group, BUN and Scr in each treatment group and model control group showed no significant changes, the difference was not statistically significant. At the end of treatment, compared with the model control group, the expression of TIMP-1 mRNA was significantly down-regulated and the expression of MMP-9 mRNA was significantly up-regulated in all treatment groups (P <0.05). There was no significant difference in the expression of TIMP-1 and MMP-9 . Conclusion: The renal protective effect of safflower yellow injection on MN rats may be related to its ability to down-regulate TIMP-1 and up-regulate the expression of MMP-9.