基于JAK2/STAT1/STAT3通路探讨化瘀通络中药改善db/db小鼠肾组织损伤的研究  

Amelioration of Renal Tissue Damage in db/db Mice by Chinese Stasis-resolving and Collateral-dredging Medicinal Based on JAK2/STAT1/STAT3 Pathway

作　　者：任改燕 张学琴 方敬 马赟[2] 申旭阳 张天伟 吴媛 娄菲菲 陈志强[2] REN Gaiyan;ZHANG Xueqin;FANG Jing;MA Yun;SHEN Xuyang;ZHANG Tianwei;WU Yuan;LOU Feifei;CHEN Zhiqiang(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Hebei General Hospital,Shijiazhuang 050057,China)

机构地区：[1]河北中医药大学,河北石家庄050200 [2]河北省中医院,河北石家庄050011 [3]河北省人民医院,河北石家庄050057

出　　处：《河北中医药学报》2025年第2期8-12,17,共6页Journal of Hebei Traditional Chinese Medicine and Pharmacology

基　　金：国家自然科学基金面上项目(82274504);河北省重点研发计划项目(20377711D);河北省中西医结合肝肾病证研究重点实验室开放课题(A202103);河北省中医药管理局科研计划项目(2021167)。

摘　　要：目的:观察化瘀通络中药对db/db小鼠肾脏损伤的改善作用。方法:16只雄性8周龄db/db小鼠及8只同背景下db/m小鼠[作为对照组(C组)],适应性喂养1周后,测小鼠尿微量白蛋白/肌酐比值(UACR),显示糖尿病肾病(diabetic nephropathy,DN)小鼠模型成立后,将db/db小鼠随机分为2组:模型组(M组)、化瘀通络中药组(H组)。C组、M组分别予纯水灌胃,H组予化瘀通络中药灌胃,连续干预13周。于13周末检测小鼠尿液微量蛋白/肌酐比值(UACR)、血胱抑素C(Cys-C)、肌酐(Scr)、尿素氮(BUN)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)水平;光镜观察小鼠肾组织病理改变;采用ELISA法检测血清中白介素-6(IL-6)及单核细胞趋化蛋白-1(MCP-1)水平;Western blot检测肾组织中IL-6蛋白表达水平及酪氨酸蛋白激酶2(JAK2)/信号传导及转录激活因子1(STAT1)/信号传导及转录激活因子3(STAT3)通路关键蛋白的表达水平。结果:与C组相比,M组小鼠尿液UACR、血Cys-C、TG、LDL-C均增多(P<0.05),Scr、BUN、HDL-C未见明显变化;光镜下可见肾小球系膜细胞和细胞外基质增生,肾小球基底膜增厚,肾小球和肾间质轻度纤维化;ELISA结果显示血清中IL-6、MCP-1蛋白表达水平均增高(P<0.05);Western blot结果显示肾组织中IL-6蛋白表达水平及p-JAK2/JAK2、p-STAT1/STAT1、p-STAT3/STAT3比值均增高(P<0.05)。与M组相比,H组小鼠尿液UACR、血Cys-C、TG、LDL-C均减少(P<0.05),Scr、BUN、HDL-C未见明显变化;光镜下可见肾脏病理改变得到改善;ELISA结果显示血清中IL-6、MCP-1蛋白表达水平均降低(P<0.05);Western blot结果显示H组小鼠肾组织中IL-6蛋白表达水平及p-JAK2/JAK2、p-STAT1/STAT1、p-STAT3/STAT3比值均降低(P<0.05)。结论:化瘀通络中药可能通过抑制JAK2/STAT1/STAT3通路减轻炎症反应,延缓DN进展。Objective:To observe the ameliorative effect of Chinese Stasis-resolving and Collateral-dredging Medicinal on renal damage in db/db mice.Methods:Sixteen male db/db mice at 8 weeks of age and 8 db/m mice of the same background[serving as the control group(Group C)]were used.After 1 week of adaptive feeding,the urinary microalbumin/creatinine ratio(UACR)of the mice was measured.After the mouse model of diabetic nephropathy(DN)was successfully established,the db/db mice were randomly divided into 2 groups:the model group(Group M)and the group treated with Chinese stasis-resolving and collateral-dredging medicinal(Group H).Group C and Group M were respectively given intragastric administration of pure water,and Group H was given intragastric administration of Chinese stasis-resolving and collateral-dredging medicinal.The intervention was carried out continuously for 13 weeks.At the end of the 13th week,the levels of UACR in the urine,serum cystatin C(Cys-C),serum creatinine(Scr),blood urea nitrogen(BUN),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)of the mice were detected;the pathological changes of the renal tissues of the mice were observed under a light microscope;the levels of interleukin-6(IL-6)and monocyte chemoattractant protein-1(MCP-1)in the serum were detected by the ELISA method;the expression level of IL-6 protein in the renal tissues and the expression levels of key proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 1(STAT1)/signal transducer and activator of transcription 3(STAT3)pathway were detected by Western blot.Results:Compared with Group C,the urinary UACR,serum Cys-C,TG and LDL-C levels in Group M increased(P<0.05),while there were no significant changes in Scr,BUN and HDL-C levels.Under the light microscope,hyperplasia of mesangial cells and extracellular matrix in the glomeruli,thickening of the glomerular basement membrane,and mild fibrosis of the glomeruli and renal interstitium were observed.Th

关 键 词：糖尿病肾病 化瘀通络中药 DB/DB小鼠 JAK2/STAT1/STAT3信号通路 炎症 

分 类 号：R285.5[医药卫生—中药学]