| 任凌燕,朱鸣,朱华艳,丁敏,费丹峰,霍丽霞,王霄一.雷公藤甲素通过调控TLR/NF-κB信号通路对早期糖尿病肾病足细胞的作用研究[J].浙江中西医结合杂志,2020,30(3): |
| 雷公藤甲素通过调控TLR/NF-κB信号通路对早期糖尿病肾病足细胞的作用研究 |
| Effect of Triptolide on podocytes by regulating TLR/NF-κB signaling pathway in early diabetic nephropathy |
| 投稿时间：2019-11-24 修订日期：2020-02-05 |
| DOI： |
| 中文关键词: 雷公藤甲素 TLR/NF-κB信号通路 早期糖尿病肾病 足细胞 |
| 英文关键词:Triptolide TLR/NF-κB signaling pathway Early diabetic nephropathy Podocyte |
| 基金项目:浙江省医药卫生科技计划项目（No.2016KYA172，2017KY639）;浙江省湖州市科技计划项目（No.2016GY27） |
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| 中文摘要: |
| 目的 观察雷公藤甲素治疗糖尿病肾病小鼠的疗效，并探讨其通过Toll-样受体（TLR）/核因子κB（NF-κB）信号通路对糖尿病肾病足细胞的作用机制。方法：9周龄db/m和db/db雄性小鼠分为db/m正常对照组（等量0.9%生理盐水）、db/db糖尿病对照组（等量0.9%生理盐水）、替米沙坦治疗组[5mg /( kg.d)]、雷公藤甲素组 [50ug /( kg.d) ]，治疗8周。记录各组小鼠一般情况、24h尿蛋白定量、体质量、肾脏指数和血生化指标。光镜观察肾小球病变情况。WT1免疫组化计算足细胞数量。Western blot检测肾脏足细胞相关蛋白Nephrin、Podocin以及肾脏组织TLR4和NF-κB蛋白定量表达。结果 与糖尿病对照组比较，经雷公藤甲素组小鼠治疗后24h尿蛋白定量[(98.28±11.10)mg/24h比(239.89±44.26)mg/24h]、血清肌酐[(38.82±3.66)μmol/L 比(45.32±7.63)μmol/L]、总胆固醇[(3.05±0.54)mmol/L比(4.00±0.67)mmol/[及甘油三酯[(1.23±0.15)mmol/L比(2.09±0.48)mmol/L]均明显下降(P 均< 0.01)，血清白蛋白水平上升[(39.21±4.33)g/L比(25.46±1.54)g/L，P < 0.01]，肾小球肥大和足细胞损伤减轻，Nephrin[ (2.05±0.44)比(1.15±0.22)]、Podocin[(1.32±0.25)比(0.72±0.20)]蛋白表达量上升；(P 均< 0.01)，TLR4[ (0.37±0.04)比(0.61±0.04)]和NF-κB[ (0.41±0.05)比(0.76±0.06)]蛋白表达量下降(P 均< 0.01)。结论 雷公藤甲素可能通过抑制TLR/NF-κB信号通路相关因子的表达，减轻糖尿病肾病小鼠足细胞损伤，减低蛋白尿，保护肾功能，起到治疗糖尿病肾病的作用。 |
| 英文摘要: |
| Abstract Objective To observe the efficacy of triptolide in the treatment of diabetic nephropathy mice and to explore mechanism of triptolide on podocytes by regulating Toll-like receptors(TLR)/Nuclear factor-kappaB(NF-κB) signaling pathway in diabetic nephropathy. Methods Nine weeks-old db/m and db/db mice were divided into four groups: db/m mice were treated with saline, db/db mice were treated with saline, db/db mice were treated with telmisartan[5mg /( kg.d)], db/db mice were treated with triptolide [50ug /( kg.d) ], and each group had 6 mice.To observe the general situation of mice in each group. At the 8th week, the levels of 24 hour urinary protein, body weight, kidney index and blood biochemistry indicators were measured. Glomerular lesions were observed by light microscopic. Number of podocytes was counted by WT1 immunohistochemistry method. The Nephrin, Podocin, TLR4 and NF-κB protein levels were calculated by Western blot. Results After treatment with triptolide in db/db mice, the levels of 24 hour urinary protein, blood creatinine, blood lipids and blood glucose were significantly decreased [24h urinary protein: (98.28±11.10) mg/24h vs (239.89±44.26) mg/24h; blood creatinine: (38.82±3.66) μmol/L vs (45.32±7.63) μmol/L; blood lipids: (3.05±0.54) mmol/Lvs (4.00±0.67) mmol/L; blood lipids: (1.23±0.15) mmol/L vs (2.09±0.48) mmol/L, P<0.01],but the levels of albumin was significantly increased [(39.21±4.33) g/L vs (25.46±1.54) g/L, P<0.01]. Glomerular cell hypertrophy and podocyte injury was alleviated in triptolide group. The Nephrin and Podocin protein levels were significantly improved [Nephrin: (2.05±0.44) vs (1.15±0.22); Podocin: (1.32±0.25) vs (0.72±0.20), P< 0.01], meanwhile the TLR4 and NF-κB protein levels were significantly decreased by triptolide treatment [TLR4: (0.37±0.04) vs (0.61±0.04); NF-κB: (0.41±0.05) vs (0.76±0.06), P< 0.01]. Conclusions Triptolide might attenuate the expression of TLR/NF-κB signaling pathway-related factors, allieved podocyte injury, reduced proteinuria, protected renal function in diabetic nephropathy mice and played a vital role in the treatment of diabetic nephropathy. |
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