Page 54 - 《中国药房》2023年13期

通心络胶囊对糖尿病肾病模型大鼠肾纤维化的干预作用
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白 璐 ，沈士朋，王 倩，李 敏，郭 帅，刘茂东（河北医科大学第三医院肾内科，石家庄 050051）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2023）13-1584-06
DOI 10.6039/j.issn.1001-0408.2023.13.08

摘 要 目的 探讨通心络胶囊对糖尿病肾病（DN）模型大鼠肾纤维化的干预作用及机制。方法 随机选取8只大鼠作为对照组
（普通饲料），其余大鼠给予高糖高脂饲料饲养联合腹腔注射链脲佐菌素（35 mg/kg）建立DN模型。造模成功的大鼠随机分为模型
组（纯化水）、厄贝沙坦组（阳性对照，14.12 mg/kg）、通心络胶囊组（0.3 g/kg），其中模型组12只，其余2组各11只。各组大鼠灌胃相
应药物或水，每天给药1次，连续16周。末次给药后，检测大鼠空腹血糖、24 h尿蛋白（24 h UTP）；观察大鼠肾皮质病理形态学变
化；检测大鼠血清中纤溶酶原激活物（PA）、纤溶酶原激活剂抑制因子 1（PAI-1）水平；检测大鼠肾皮质中转化生长因子 β1 （TGF-
β1 ）、Ⅳ型胶原蛋白（COL-Ⅳ）、Wnt4、β-连环蛋白（β-catenin） mRNA表达水平；观察或检测大鼠肾皮质中TGF-β1、COL-Ⅳ、黏着斑
激酶（FAK）、整合素连接激酶（ILK）、E-钙黏蛋白（E-cadherin）、PA、PAI-1、Wnt4、β-catenin蛋白沉积或表达水平。结果 与模型组比
较，通心络胶囊组大鼠24 h UTP均显著降低（P＜0.05）；肾皮质病理损伤及纤维化程度均减轻；血清和肾皮质中PA表达水平均显
著升高、PAI-1表达水平均显著降低（P＜0.05）；肾皮质中TGF-β1、COL-Ⅳ蛋白沉积及相应mRNA表达水平均显著减少或降低（P＜
0.05），ILK、FAK蛋白沉积均减少，E-cadherin蛋白沉积均增多，Wnt4、β-catenin 蛋白和mRNA的表达水平均显著降低（P＜0.05）。
结论 通心络胶囊能减轻DN模型大鼠肾组织病理损伤及肾纤维化程度，减少细胞外基质沉积；其机制可能与调节纤溶系统活性，
降低ILK、FAK表达，抑制Wnt/β-catenin信号通路激活有关。
关键词 糖尿病肾病；通心络胶囊；纤溶系统；肾纤维化；Wnt/β-catenin信号通路

Intervention effect of Tongxinluo capsule on renal fibrosis in diabetic nephropathy rats
BAI Lu，SHEN Shipeng，WANG Qian，LI Min，GUO Shuai，LIU Maodong（Dept. of Nephrology， the Third
Hospital of Hebei Medical University， Shijiazhuang 050051， China）

ABSTRACT OBJECTIVE To explore the intervention effect and related mechanism of Tongxinluo capsule on renal fibrosis in
rats with diabetic nephropathy （DN）. METHODS Eight rats were selected as control group （ordinary feed）， the remaining rats
were given high-glucose and high-fat diet combined with ip injection of streptozotocin （35 mg/kg） to induce DN model. Model rats
were randomly divided into model group （purified water）， irbesartan group （positive control， 14.12 mg/kg） and Tongxinluo
capsule group （0.3 g/kg）， including 12 rats in the model group and 11 rats for each of the other two groups. All groups were
given relevant medicine or water intragastrically， once a day， for 16 consecutive weeks. After the last medication， fasting blood
glucose and 24 h urinary total protein （24 h UTP） were detected. Pathological changes in renal cortex of rats in each group were
observed. Serum levels of tissue-type plasminogen activator （PA） and plasminogen activator inhibitor 1 （PAI-1） were measured.
mRNA expressions of transforming growth factor-β1 （TGF-β1 ）， type Ⅳ collagen（COL-Ⅳ）， Wnt4 and β-catenin in renal cortex of
rats were detected. The protein depositions or expressions of TGF- β1， COL- Ⅳ ， focal adhesion kinase （FAK）， integrin-linked
kinase （ILK）， E-cadherin， PA， PAI-1， Wnt4 and β -catenin in renal cortex of rats were observed or determined. RESULTS
Compared with model group， 24 h UTP of rats in Tongxinluo capsule group were all significantly reduced （P＜0.05）； pathological
damage and fibrosis of renal cortex were relieved； the expression of PA in serum and renal cortex was significantly increased，
while PAI-1 level was significantly reduced （P＜0.05）； the depositions of COL-Ⅳ and TGF-β1 in renal cortex were all reduced，
and corresponding mRNA expression was decreased significantly （P＜0.05）； the depositions of ILK and FAK were decreased，
while the deposition of E-cadherin was increased； protein and mRNA expressions of Wnt4 and β-catenin were significantly reduced
（P＜0.05）. CONCLUSIONS Tongxinluo capsule can relieve pathological damage to renal tissue and renal fibrosis of DN model
rats， and reduce extracellular matrix deposition. The mechanism may be related to regulation of fibrinolytic system activity， the
decrease of ILK and FAK expression， and inhibition of Wnt/β-catenin signaling pathway.
KEYWORDS diabetic nephropathy； Tongxinluo capsule； fibrinolytic system； renal fibrosis； Wnt/β-catenin signaling pathway

糖尿病肾病（diabetic nephropathy，DN）是糖尿病常
Δ 基金项目 河北省中医药管理局科研计划项目（No.2019131，No.
见而严重的微血管病变之一，以持续蛋白尿及进行性肾
2022408）
功能恶化为临床表现，主要的病理特征为肾小球基底膜
＊第一作者 副主任医师，博士。研究方向：肾脏病的中西医结合
治疗。E-mail：bailu2011@126.com 弥漫性增厚、系膜基质增生、Kimmelstiel-Wilson 结节形

· 1584 · China Pharmacy 2023 Vol. 34 No. 13 中国药房 2023年第34卷第13期