茯苓多糖对db/db小鼠肾脏保护作用及其对p38 MAPK/PPAR-γ信号通路的影响  

Renal Protection Action of Pachymaran and Effects on p38 MAPK/PPAR-γ Signaling Pathway in db/db Mice

作　　者：李佳丹 周迪夷 LI Jiadan;ZHOU Diyi(The Fourth Clinical Medical College of Zhejiang Chinese Medicine University,Hangzhou First People’sHospital,Hangzhou,Zhejiang 310053;Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310003)

机构地区：[1]浙江中医药大学第四临床医学院,杭州市第一人民医院,浙江杭州310053 [2]浙江省中西医结合医院,浙江杭州310003

出　　处：《中国中医药科技》2019年第3期346-350,共5页Chinese Journal of Traditional Medical Science and Technology

基　　金：国家自然科学基金(8170150267)

摘　　要：目的:探讨茯苓多糖对db/db小鼠的肾脏保护作用及p38丝裂原活化蛋白激酶(p38 MAPK)/过氧化物酶体增殖物激活受体-γ(PPAR-γ)信号通路的调控作用。方法:6只C57BL/KsJ-db/+小鼠作为正常对照组,28只db/db小鼠随机分为模型组、茯苓多糖低剂量组、茯苓多糖高剂量组、阳性药组(厄贝沙坦),每组6只,连续给药8周。每2周检测1次FBG;8周末,眼内眦取血,生化法检测血清肌酐(SCr)和尿素氮(BUN);麻醉处死,取双肾,称重,计算肾脏指数;HE染色,光镜观察肾组织病理变化;Western blot法检测肾组织p-p38 MAPK、p38 MAPK和PPAR-γ的表达。结果:与正常组相比,模型组小鼠FBG、血清SCr及BUN水平、肾脏指数升高(P<0.05);与模型组相比,茯苓多糖组小鼠FBG水平显著降低、血清SCr及BUN水平、肾脏指数降低(P<0.05);HE染色结果显示模型组小鼠肾脏出现明显病理损伤,茯苓多糖组能改善小鼠肾脏损伤;Western blot结果显示随着茯苓多糖浓度的升高,肾组织p-p38 MAPK水平逐渐降低,PPAR-γ水平逐渐升高。结论:茯苓多糖能明显改善db/db小鼠肾脏损伤,其机制可能与p38 MAPK磷酸化受到抑制及PPAR-γ通路被激活有关。Objective: To observe the renal protection action of Pachymaran and regulation effects on p38 mitogen-activated protein kinase (p38 MAPK)/peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling pathway in db/db mice. Methods: Six male C57BL/KsJ-db/+ mice were used as normal control group.,28 male db/db mice were randomly divided into model group;Pachymaran low dose group (6.0 mg·kg^-1 ·d^-1 ), Pachymaran high dose group (12.0 mg·kg -1 ·d -1 ), positive drug group (irbesartan 16.0 mg· kg^-1 ·d^-1 ), with 6 mice in each group. Drugs were administrated for 8 weeks. The fasting blood glucose (FBG) were measured every 2 weeks. At the end of 8 weeks, blood was got from the eye, the SCr and BUN were detected by biochemical method. Both kidneys were taken and weighed to calculate the renal hypertrophy index. The pathological changes of kidney were observed by hematoxylin-eosin (HE) staining.The expressions of p-p38 MAPK, p38 MAPK and PPAR-γ in kidney tissues were detected by Western blot. Results: Compared with the normal group, the FBG, SCr, BUN and renal hypertrophy index were significantly increased ( P <0.05) in the model group. Compared with the model group, the FBG in the Pachymaran group increased at a lower rate, and the SCr, BUN and renal hypertrophy index were significantly decreased ( P <0.05). HE staining results showed that renal glomerular injury and structural changes were observed in the model group, but Pachymaran can improve the injury on kidney. Western blot results showed that with the increase of Pachymaran concentration, the level of p-p38 MAPK in kidney tissue decreased gradually, and the level of PPAR-γ increased gradually. Conclusion: Pachymaran can significantly improve kidney damage in db/db mice, and its mechanism may be related to inhibition of p38 MAPK phosphorylation and activation of PPAR-γ pathway.

关 键 词：茯苓多糖 糖尿病肾病 血糖 肾功能 病理变化 p38丝裂原活化蛋白激酶/过氧化物酶体增殖物激活受体-γ信号通路 DB/DB小鼠 

分 类 号：R285.5[医药卫生—中药学]