| 摘要: |
| 目的 探讨帕立骨化醇对糖尿病肾病（DKD）肾小管上皮间充质转化（EMT）的作用及内在机制。方法 将24 只SD
大鼠按随机数字表法分为帕立骨化醇干预组（P 组）、糖尿病肾病组（D 组）和正常对照组（C 组），每组各8 只。P 组和D 组大鼠腹腔注射链脲佐菌素65mg/kg建立糖尿病肾病模型，造模成功后第2天P 组腹腔注射帕立骨化醇（溶于丙二醇中）0.4滋g/kg，3 次/ 周，D 组予等体积丙二醇；C组仅予等体积丙二醇。4 周后测血、尿生化指标；进行肾脏病理学检查；免疫组化及Western blot 技术检测肾组织E- 钙粘蛋白（E-cadherin）、α- 平滑肌肌动蛋白（α-SMA）、纤连蛋白（FN）、转化生长因子-β1（TGF-β1）及Klotho 的表达，并进行指标间的相关性分析。结果 D组大鼠血清肌酐（Scr）、血尿素氮（BUN）及24 h尿蛋白水平均高于C 组，P 组均低于D 组（均P＜
0.05）。C 组大鼠肾小管结构完整清晰，无明显病理改变；D 组可见肾小管间质局部炎症细胞浸润，肾小管上皮细胞脱落，小管扩张，基底膜断裂；P 组肾小管间质病理改变较D 组减轻。D 组大鼠肾组织E-cadherin 与Klotho表达低于C组，而P组高于D组（均P＜0.05）；与C 组比较，D 组大鼠肾组织α-SMA、FN 及TGF-β1 表达增加，而P 组表达均较D 组减少（均P＜0.05）。Klotho 表达与E-cadherin呈正相关（r=0.924，P＜0.05），而与α-SMA、FN 及TGF-β1 均呈负相关（r=-0.806、-0.623、-0.856，均P＜0.05）。结论 帕立骨化醇可抑制糖尿病肾病大鼠肾小管上皮EMT，其作用可能与增加肾组织Klotho表达，同时减少TGF-β1合成相关。 |
| 关键词: 帕立骨化醇 糖尿病肾病 上皮间充质转化 转化生长因子-β1 Klotho |
| DOI： |
| 分类号: |
| 基金项目:浙江省医药卫生科研基金；宁波市自然科学基金 |
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| Effect of paricalcitol on tubular epithelial mesenchymal transition in diabetic kidney disease |
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WANG Lailiang, LUO Qun, CAI Kedan, ZHOU Fangfang, GAO Yanhong
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Ningbo Second Municipal Hospital
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| Abstract: |
| Objective To investigate the effect of parlicalcitol on tubular epithelial mesenchymal transition (EMT)and underlying mechanism in diabetic kidney disease (DKD). Methods DKD was induced by single intraperitoneal injection of 65 mg/kg streptozotocin(STZ) in 16 Sprague Dawley (SD) rats, then the animals were randomly divided into group P and group D with 8 in each. Rats in group P received intraperitoneal injection of paricalcitol(0.4μg·kg-1) in propylene glycol three times a week; rats in group D received intraperitoneal injection of same volume of propylene glycol; 8 rats in group C
served as normal control and received propylene glycol as in group D. Blood, urine and renal tissue samples were collected after 4 weeks intervention of paricalcitol or vehicles. Biochemical indexes were measured, renal tissue was examined histopathologically and the expression of E-cadherin, alpha-smooth muscle actin (α-SMA), fibronectin (FN), transforming growth factor-β1 (TGF-β1) and klotho in renal tissue were measured with immunohistochemistry and Western blotting, respectively.In addition, the correlation among the indexes was analyzed. Results Scr, BUN and 24 h urine protein increased significantly in group D compared with group C, while decreased in group P compared with group D (all P＜0.05).Local inflammatory cell infiltration, tubular epithelial cell detachment, tubular expansion and basement membrane rupture were observed in group D, but attenuated in group P compared with group C. The expression of E-cadherin and klotho decreased,while α-SMA, FN and TGF-β1 increased in group D compared with group C (all P＜0.05). Compared with D, the expression of E-cadherin and klotho increased, while α-SMA, FN and TGF-β1 decreased in group P (all P＜0.05). The
expression of klotho was negatively correlated with α-SMA, FN and TGF-β1, while was positively correlated with E-cadherin(r=-0.806, P＜0.05; r=-0.623, P＜0.05; r=-0.856, P＜0.05; r=0.924, all P＜0.05). Conclusion Paricalcitol can inhibittubular EMT in DKD, which may be associated with its effect of upregulating Klotho expression, and inhibiting TGF-β1 synthesis. |
| Key words: Paricalcitol Diabetic kidney disease Epithelial mesenchymal transition TGF-β1 Klotho |
