抗纤灵冲剂对肾间质纤维化大鼠结缔组织生长因子蛋白表达的影响  

Effects of Kangxianling Granules on expression of connective tissue growth factor protein in rats with renal interstitial fibrosis

作　　者：张新志[1] 钱玲[2] 吴锋[1] 董飞侠 黄迪[4] 何立群[1] ZHANG Xin-zhi;QIAN Lin;WU Feng;DONG Fei-xia;HUANG Di;HE Li-qun(Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China;Shanghai East Hospital Affiliated to Tongji University,Shanghai 200123,China;Wenzhou Hospital of Chinese Medicine Affiliated to Zhejiang Chinese Medical University,Wenzhou 325000,China;TCM Institute of Kidney Disease,Shanghai University of Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院肾病科,上海200021 [2]同济大学附属东方医院,上海200123 [3]浙江中医药大学附属温州中医院,温州325000 [4]上海中医药大学中医肾病研究所,上海201203

出　　处：《中华中医药杂志》2020年第7期3682-3685,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.30873259);上海市优秀学科带头人培养计划资助(No.08XD14039);何立群上海市名老中医学术经验研究工作室(No.SHGZS-2017027);肝肾疾病病证教育部重点实验室,上海市中医临床重点实验室(No.14DZ2273200);海派中医流派传承研究基地(No.ZYSNXDCCYJXYY);上海市浦东新区卫生系统重点学科群建设资助(No.PWZxq2017-07)。

摘　　要：目的:从结缔组织生长因子(CTGF)蛋白表达的角度,研究抗纤灵冲剂干预肾间质纤维化的作用机制。方法:将96只SPF级SD大鼠随机分为假手术组24只,造模组72只,造模组大鼠应用UUO法制备肾间质纤维化大鼠模型,造模成功后分为模型组、抗纤灵组、氯沙坦组。药物干预后分批处死,留取尿液、左侧肾组织。应用免疫组化法测定CTGF在肾间质细胞及肾小管基底膜的蛋白表达;用放射免疫法测定尿β2-MG水平。结果:与假手术组比较,模型组大鼠CTGF蛋白表达和尿β2-MG水平显著增加(P<0.01,P<0.05);与模型组比较,抗纤灵组和氯沙坦组各时间点CTGF蛋白表达显著减少(P<0.05,P<0.01),抗纤灵组各时间点尿β2-MG水平显著降低(P<0.01,P<0.05);氯沙坦组尿β2-MG水平7d时显著降低(P<0.01);抗纤灵组各时间点CTGF蛋白表达显著低于氯沙坦组(P<0.01);抗纤灵组14d及28d时尿β2-MG水平显著低于氯沙坦组(P<0.01)。结论:抗纤灵冲剂通过调控CTGF基因表达,下调CTGF在肾间质细胞及肾小管基底膜的蛋白表达,从而达到改善肾间质纤维化、保护肾小管功能的作用。Objective:To study the mechanism of Kangxianling Granules in intervention renal interstitial fibrosis from the expression of connective tissue growth factor(CTGF)protein.Methods:A total of 96 SPF Sprague-Dawley rats were randomly divided into sham-operated group(n=24)and model group(n=72).The model group was prepared by UUO method,they were randomly divided into model group,Kangxianling(KXL)group and Losartan group after successful modeling.After drug intervention,they were killed in batches,the urine and left renal tissue were collected.The protein expression of CTGF in renal stromal cells and basement membrane of renal tubules was determined by immunohistochemistry,and urine β2-MG levels were determined by radioimmunoassay.Results:Compared with the sham-operated group,the expression of CTGF protein and the level of β2-MG in the model group were significantly increased(P<0.01,P<0.05).Compared with the model group,the expression of CTGF protein in the KXL group and losartan group were significantly reduced at each time point(P<0.05,P<0.01).The level of β2-MG was significantly reduced in KXL group at each time point(P<0.01,P<0.05).The level ofβ2-MG in losartan group decreased significantly at 7d(P<0.01).The expression of CTGF protein in KXL group at each time point was significantly lower than that in losartan group(P<0.01).At 14d and 28d,the level ofβ2-MG in KXL group was significantly lower than that in losartan group(P<0.01).Conclusion:Kangxianling Granules can improve renal interstitial fibrosis and protect renal tubular function by regulated the expression of CTGF gene and down-regulated the protein expression of CTGF in renal stromal cells and basement membrane of renal tubules.

关 键 词：抗纤灵冲剂 结缔组织生长因子 尿Β2-微球蛋白 肾络癥瘕 肾间质纤维化 

分 类 号：R285.5[医药卫生—中药学]