黄芩苷调节galectin-3/Akt/GSK-3β/Snail信号通路改善慢性肾脏病大鼠的肾纤维化机制  

Baicalin improves renal fibrosis in rats with chronic kidney disease by regulating the galectin-3/Akt/GSK-3β/Snail signaling pathway

作　　者：刘倩盼 邵翔 李玉婷 刘曼 谭鹏 王越 LIU Qianpan;SHAO Xiang;LI Yuting(Department of Nephrology,Kowloon Hospital,Shanghai Jiao Tong University School of Medicine,Jiangsu,Suzhou 215129,China;不详)

机构地区：[1]上海交通大学医学院苏州九龙医院肾内科,江苏省苏州市215129 [2]上海交通大学医学院苏州九龙医院中心实验室,江苏省苏州市215129 [3]上海交通大学医学院苏州九龙医院老年科,江苏省苏州市215129

出　　处：《河北医药》2024年第15期2261-2265,共5页Hebei Medical Journal

基　　金：苏州市科学发展计划项目(编号:SYSD2019070)。

摘　　要：目的 探讨黄芩苷调节半乳糖凝集素3(galectin-3)/蛋白激酶B(Akt)/糖原合成酶激酶(GSK-3β)/Snail信号通路对慢性肾脏病大鼠肾纤维化的影响。方法 采用腺嘌呤诱导制备慢性肾脏病大鼠肾纤维化模型,随机将健康雄性SD大鼠分为对照组、模型组、阳性药物(氯沙坦,9 mg/kg)组、低剂量黄芩苷组(20 mg/kg)、中剂量黄芩苷组(40 mg/kg)、高剂量黄芩苷组(80 mg/kg),模型组和对照组给予等体积0.9%氯化钠溶液灌胃。30 d后,检测6组大鼠血清尿素氮(BUN)和血肌酐(Scr)水平;Masson染色检测肾脏组织胶原分布面积;苏木精-伊红(HE)染色观察肾脏组织病理变化;免疫组化学法检测肾脏组织中α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原A1(CoLIA1)表达;蛋白印迹(Western blot)法分析肾脏组织中galectin-3、p-Akt/Akt、p-GSK-3β/GSK-3β、Snail表达情况。结果 与对照组比较,模型组大鼠肾脏损伤严重并伴有黑色腺嘌呤代谢物结晶沉积,胶原纤维增多,肾脏组织胶原分布面积、α-SMA、CoLIA1、Scr、BUN、galectin-3、p-Akt/Akt、p-GSK-3β/GSK-3β、Snail水平升高(P<0.05);与模型组比较,阳性药物组、黄芩苷低、中和高剂量组大鼠肾间质、肾小球和肾小管病变明显减轻,腺嘌呤代谢物结晶和纤维化组织减少,肾脏组织胶原分布面积、α-SMA、CoLIA1、Scr、BUN、galectin-3、p-Akt/Akt、p-GSK-3β/GSK-3β、Snail水平降低(P<0.05)。结论 黄芩苷可能通过抑制galectin-3/Akt/GSK3β/Snail信号通路,进而改善慢性肾脏病大鼠肾纤维化。Objective To investigate the impact of baicalin on renal fibrosis in rats with chronic kidney disease by regulating the galectin-3/protein kinase B(Akt)/glycogen synthase kinase(GSK-3β)/Snail signaling pathway.Methods The renal fibrosis model in rats with chronic kidney disease was created by adenine induction.The healthy male Sprague-Dawley(SD)rats were randomly grouped into control group,model group,positive drug group(treatment of losartan 9mg/kg),low-dose baicalin group(treatment of baicalin 20mg/kg),medium-dose baicalin group(treatment of baicalin 40mg/kg),and high-dose baicalin group(treatment of baicalin 80mg/kg).Drug administration was given through oral gavage,and rats in the model group and control group were given an equal volume of normal saline by gavage.After 30 days,serum urea nitrogen(BUN)and serum creatinine(Scr)levels of rats were measured.The collagen distribution area of kidney tissues was measured by Masson staining.Pathological changes of kidney tissues were observed by hematoxylin & eosin(H&E)staining.Positive expressions of α-smooth muscle actin(α-SMA)and type Ⅰ collagen A1(CoLIA1)in kidney tissues were detected by immunohistochemistry.Western blot was applied to analyze the protein expressions of galactin-3,p-Akt/Akt,p-GSK-3β/GSK-3β and Snail in kidney tissues.Results Compared with the control group,rats in the model group had severe renal injury,deposition of black adenine metabolite crystals,significantly increased collagen fibers,enlarged collagen distribution area of kidney tissues,and upregulated α-SMA,CoLIA1,Scr,BUN,galectin-3,p-Akt/Akt,p-GSK-3β/GSK-3β,and Snail(P<0.05).Compared with the model group,the pathological changes of renal interstitium,glomerulus and renal tubule in the positive drug group,low-dose,medium-dose and high-dose baicalin group were significantly alleviated,with the significantly reduced crystallization of adenine metabolites and fibrotic tissues,smaller collagen distribution area of kidney tissues,and downregulated α-SMA,CoLIA1,Scr,BUN,galectin-3,p-A

关 键 词：黄芩苷 慢性肾脏病 肾纤维化 半乳糖凝集素3/蛋白激酶B/糖原合成酶激酶/Snail信号通路 

分 类 号：R692[医药卫生—泌尿科学]