芪地糖肾方对糖尿病肾病小鼠肾脏病变及血清Klotho、MMP-9/TIMP-1的影响  

Effect of Qi Di Tang Shen decoction on renal pathology and serum Klotho,MMP-9/TIMP-1 in diabetic nephropathy mice

作　　者：史扬 周盈 安至超 郭燕 郑毅成 董昭熙 柳红芳[1] SHI Yang;ZHOU Ying;AN Zhichao;GUO Yan;ZHENG Yicheng;DONG Zhaoxi;LIU Hongfang(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China;Fangshan Hospital of Beijing University of Chinese Medicine,Beijing 102400,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学房山医院,北京102400

出　　处：《现代中西医结合杂志》2023年第8期1042-1046,1102,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金项目(82004297);北京市自然科学基金项目(7212180);国家中医药管理局国家中医临床研究基地业务建设科研专项课题(JDZX2015305)。

摘　　要：目的 探究芪地糖肾方对糖尿病肾病小鼠肾脏病变及血清Klotho、基质金属蛋白酶-9(MMP-9)/组织金属蛋白酶抑制剂-1(TIMP-1)的影响。方法 将36只14周龄db/db小鼠随机分为模型组、缬沙坦组、芪地糖肾方组,每组12只。选取12只14周龄db/m小鼠作为正常组。缬沙坦组给予10.29 g/kg缬沙坦水溶液灌胃,芪地糖肾方组给予3.33 g/kg芪地糖肾方颗粒水溶液灌胃,正常组及模型组给予等量的生理盐水灌胃,均1次/d,连续12周。免疫酶联吸附法检测尿微量白蛋白水平,计算12 h尿白蛋白水平;称小鼠体重、左肾重,计算肾重体重比值;免疫酶联吸附法检测血清Klotho、MMP-9、TIMP-1水平,计算MMP-9/TIMP-1;电镜、光镜下观察肾脏组织病理形态。结果 与正常组比较,模型组小鼠肾重体重比值、血清Klotho水平均明显降低(P均<0.05),12 h尿白蛋白水平及血清MMP-9、TIMP-1水平和MMP-9/TIMP-1均明显升高(P均<0.05),肾脏超微结构紊乱,肾小球基底膜明显增厚(P<0.05)。与模型组比较,芪地糖肾方组小鼠肾重体重比值明显升高(P<0.05),缬沙坦组升高不明显(P>0.05);缬沙坦组、芪地糖肾方组小鼠血清Klotho水平均明显升高(P均<0.05),12 h尿白蛋白水平及血清MMP-9、TIMP-1水平和MMP-9/TIMP-1均明显降低(P均<0.05),肾脏超微结构病变较轻,肾小球基底膜厚度均明显降低(P均<0.05)。结论 芪地糖肾方可明显减少糖尿病肾病小鼠尿蛋白,改善肾脏病变,其机制可能与调节血清Klotho及MMP-9/TIMP-1平衡有关。Objective It is to investigate the effects of Qi Di Tang Shen decoction on the renal pathology and serum Klotho,matrix metalloproteinase-9(MMP-9)/tissue inhibitor of matrix metalloproteinase-1(TIMP-1)in diabetic nephropathy(DN)mice.Methods Thirty-six 14 week old db/db mice were randomly divided into model group,valsartan group,and Qi Di Tang Shen decocion group,with 12 mice in each group.Twelve 14 week old db/m mice were selected as the normal group.The valsartan group was given valsartan aqueous solution 10.29 g/kg by gavage,the Qi Di Tang Shen decocion group was given Qi Di Tang Shen decocion granules aqueous solution 3.33 g/kg by gavage,and the normal group and model group were given an equal amount of normal saline by gavage,all once daily,continuously treated for 12 weeks.The level of urinary albumin was detected by immunoenzyme linked assay,and the level of 12 h-urinary albumin was calculated.The weigh of body and left kidney of the mice were weighted,and the ratio of kidney weight to body weight was calculated.The levels of Klotho,MMP-9,and TIMP-1 in serum were detected by immunoenzyme linked immunosorbent assay,and MMP-9/TIMP-1 was calculated.The pathological morphology of kidney tissue was observed under electron microscopy and light microscopy.Results Compared with the normal group,the kidney weight to body weight ratio and the level of serum Klotho of the mice in the model group were significantly reduced(all P<0.05),while the levels of 12 hour urine albumin,serum MMP-9,TIMP-1,and MMP-9/TIMP-1 were significantly increased(all P<0.05),the renal ultrastructure was disrupted,and the glomerular basement membrane was significantly thickened(P<0.05).Compared with the model group,the kidney weight to body weight ratio of the mice in the Qi Di Tang Shen decoction group was significantly increased(P<0.05),while the increase in the valsartan group was not significant(P>0.05);the levels of serum Klotho of the mice in the valsartan group and Qi Di Tang Shen decoction group were significantly increased(all P<0.05),

关 键 词：芪地糖肾方 糖尿病肾病 KLOTHO 基质金属蛋白酶-9 组织金属蛋白酶抑制剂-1 肾小球基底膜 

分 类 号：R-332[医药卫生]