红花黄色素注射液对膜性肾病大鼠的肾保护作用及对基质金属蛋白酶抑制物-1、基质金属蛋白酶-9表达的影响

Effects of the safflower yellow injection on membranous nephropathy rats renal protection and on the expression of TIMP-1,MMP-9mRNA

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 the safflower yellow injection on blood biochemical indexes and the expression of tissue matrix met- alloproteinases inhibitor-1 （ TIMP-1 ）, matrix metalloproteinases 9 （ MMP-9 ） of membranous nephropathy （ MN ） rats, explore the renal protec- tive effects and possible mechanism of the safflower yellow injection on MN rats. Methods： 60 SD rats were randomly selected 10 for the normal group, the other 50 to copy the MN rat model ,then randomly divided into Model group, Benazepril group, and Safflower yellow injection group（ 6.5mg/kg, 13mg/kg,26mg/kg） ,each group was treated according to the corresponding dose ,rats in the 4th weekend testing 24 hours urinary protein quantitative （ UTP）, the serum total cholesterol （ TC ）, triglyceride （ TG ）, total protein （ TP）, albumin （ ALB ）, blood urea nitrogen （BUN） ,serum creatinine（Scr） ;observing the renal pathological morphology changes by electron microscope and immunofluorescence tech- nique, and detecting the expression of TIMP-1, MMP-gmRNA by in situ hybridization method. Results： Compared with model group, UTP,TC and TG in the treatment groups lower（ P 〈 0.05 ） ,TP and ALB in the treatment groups increased（ P 〈 0.05 ） ;and the difference in Safflower yellow injection group（ 6.5mg/kg, 13mg/kg,26mg/kg）and Benazepril group of UTP,TC ,TG ,TP and ALB have no statistical significance（ P 〉 0.05 ）. Compared with normal group, the difference of BUN and Scr in treatment groups and model group has no statistically significant （ P 〉 0.05 ）. Compared with model group, the expression of TIMP-1 mRNA significantly lower（ P 〈 0.05 ） , and the expression of MMP-9 mRNA raised （ P 〈 0.05 ） ; There was no statistically significant difference compared with Benazepril group and Safflower yellow injection group （ 6. 5mg/kg, 13mg/kg,26mg/kg）（ P 〉 0.05）. Conclusion： The renal protection of the safflower yellow injection on MN rats may be related to downgrade expression of TIMP-1 and raise the expression of MMP-9.