| 任凌燕,施占琴,杨勇,朱鸣.Kindlin-2介导TGF -β/Smads信号通路在糖尿病肾病模型小鼠肾小管间质纤维化的作用研究[J].浙江中西医结合杂志,2023,33(8): |
| Kindlin-2介导TGF -β/Smads信号通路在糖尿病肾病模型小鼠肾小管间质纤维化的作用研究 |
| Kindlin-2 Mediates TGF-β/Smads Signaling Pathway in Renal Tubulointerstitial Fibrosis in Diabetic Nephropathy MiceREN Lingyan1, WANG Xiaoyi1, SHI Zhanqin1, YANG Yong1, ZHU Ming1 |
| 投稿时间：2022-12-06 修订日期：2023-07-31 |
| DOI： |
| 中文关键词: Kindlin-2 TGF -β/Smads信号通路 糖尿病肾病 肾小管间质纤维化 |
| 英文关键词: |
| 基金项目:浙江省医药卫生科技项目[2022KY1224],湖州市科技计划项目[2017GY23] |
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| 中文摘要: |
| 目的 探讨Kindlin-2介导TGF -β/Smads信号通路在糖尿病肾病模型小鼠肾小管间质纤维化的作用研究。方法 将9周龄雄性db/db糖尿病与db/m小鼠分为糖尿病肾病组与正常对照组, 每组10 只, 经过12周的观察后将它们处死, 记录各组小鼠一般状态、尿液、体重和血生化指标, 行PAS和Masson三色染色观察肾脏病理病变情况, 免疫组织化学技术检测肾小管间质kindlin-2、TGF-β1、p-Smad3、Smad3、α-SMA、E-cadherin原位表达, RT-qPCR技术检测肾脏组织kindlin-2、TGF-β1、p-Smad3、Smad3、α-SMA、E-cadherin mRNA水平。结果 与正常对照组相比, 糖尿病肾病组小鼠24小时尿蛋白定量[(239.88±44.31) mg/24h比(20.16±6.03)mg/24h]、体重[(46.13±2.49)g比(23.47±2.19)g]、肾脏指数[(40.05±4.82) mg/g比(21.62±1.63)mg/g]、血糖[(49.86±7.51) mmol/L比(8.71±1.57) mmol/L]、血清尿素氮[(9.78±3.45) μmol/L比(6.02±1.65) μmol/L]、血清肌酐[(43.81±6.54) μmol/L比(29.53±3.19) μmol/L]、血清总胆固醇[(4.52±0.85) mmol/L比(2.62±0.38) mmol/L]及血清三酰甘油[(2.20±0.49) mmol/L比(0.91±0.25) mmol/L]水平明显增加,血清白蛋白 [(24.30±1.77) g/L比(33.87±3.20) g/L] 水平明显降低, kindlin-2[(1.41±0.17)比(0.91±0.16)]、TGF-β1[(2.66±0.55)比(0.90±0.19)]、p-Smad3[(1.26±0.27)比(0.49±0.12)]、Smad3[(1.60±0.38)比(0.85±0.13)]、α-SMA[(2.12±0.44)比(0.85±0.13)] mRNA水平明显增加, E-cadherin mRNA[(0.47±0.10)比(0.86±0.27)]明显降低。糖尿病肾病组肾小管间质病变较严重, 且kindlin-2、TGF-β1、p-Smad3、Smad3、α-SMA原位阳性表达强度明显增强, E-cadherin原位表达强度显著降低。结论 Kindlin-2有极大可能性经由介导TGF -β/Smads信号通路使糖尿病肾小管间质的纤维化情况加剧。 |
| 英文摘要: |
| Objective To investigate the role of Kindlin-2 mediating TGF-β/Smads signaling pathway in renal tubulointerstitial fibrosis in diabetic nephropathy mice. Methods Nine-week-old male db/m and db/db diabetic mice were divided into the normal control group and diabetic nephropathy group, each had 10 mice. The mice were sacrificed after 12 weeks, the general status, urine, body weight and blood biochemical indexes in each group were recorded. To observe the renal pathology by periodic acid shiff and Masson trichrome staining. Immunohistochemistry was used to detect the expression in situ of kindlin-2, TGF-β1, p-Smad3, Smad3, α-SMA and E-cadherin in the renal tubulointerstitial. mRNA levels of kindlin-2, TGF-β1, p-Smad3, Smad3, α-SMA and E-cadherin were tested by real-time quantitative PCR. Results Compared to the normal control group, 24h urinary protein [(239.88±44.31) mg/24h vs (20.16±6.03) mg/24h], body weight [(46.13±2.49) g vs (23.47±2.19) )g], renal index [(40.05±4.82) mg/g vs (21.62±1.63) mg/g], blood glucose [(49.86±7.51) mmol/L vs (8.71±1.57) mmol/L], serum urea nitrogen [(9.78±3.45) μmol/L vs (6.02±1.65) μmol/L], serum creatinine [(43.81±6.54) μmol/L vs (29.53±3.19) μmol/L], serum total cholesterol [(4.52±0.85 ) mmol/L vs (2.62±0.38) mmol/L] and serum triacylglycerol [(2.20±0.49) mmol/L vs (0.91±0.25) mmol/L] levels increased significantly, while serum albumin [(24.30±1.77 ) g/L vs (33.87±3.20) g/L] level reduced significantly. Kindlin-2[(1.41±0.17) vs (0.91±0.16)], TGF-β1[(2.66±0.55) vs (0.90±0.19)], p-Smad3[(1.26±0.27) vs (0.49±0.12)], Smad3 [(1.60±0.38) vs (0.85±0.13)], α-SMA [(2.12±0.44) vs (0.85±0.13)] mRNA levels were increased significantly, while E-cadherin mRNA [(0.47±0.10) vs (0.86±0.27)] level was reduced significantly. In diabetic nephropathy group, the renal tubulointerstitial lesions were more serious, and the positive expression intensity of kindlin-2, TGF-β1, p-Smad3, Smad3 and α-SMA in situ was significantly increased, while the expression intensity of E-cadherin in situ was significantly decreased. Conclusion It is highly possible that Kindlin-2 may aggravate the fibrosis of diabetic renal tubule interstitial by mediating TGF-β /Smads signaling pathway. |
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