·糖尿病基础研究·

　　【摘要】目的 探讨左卡尼汀对环孢素A(CsA)所致胰腺和肾脏损伤保护作用的分子机制。方法 将SD大鼠分为6组，即正常对照(VH)组、正常对照+左卡尼汀低剂量(VH+L50)组、正常对照+左卡尼汀高剂量(VH+L200)组、肾毒性(CsA)组、左卡尼汀低剂量治疗(CsA+L50)组和左卡尼汀高剂量(CsA+L200)组。检测胰腺及肾功能指标、自噬性溶酶体(LC3-II)表达、肾小管间质纤维化 (TIF)、肾脏 TGF-β1和8-羟基脱氧鸟苷 (8-OHdG)水平。 结果 CsA诱导胰腺损伤表现为血糖和HbA1c升高，血浆胰岛素水平下降，胰腺LC3-II表达升高(P<0.01)。肾脏中CsA致血肌酐、BUN升高、TIF增加(P<0.01)，该变化伴随TGF-β1、8-OHdG、LC3-II表达增加。左卡尼汀治疗对各指标均有效，LC3-II表达仅在高浓度左卡尼汀治疗下减少(P<0.05)。 结论 左卡尼汀对CsA所致胰腺和肾脏损伤有保护作用。

　　【关键词】左卡尼汀;环孢素A;转化生长因子β1;8-羟基脱氧鸟苷;自噬

L-carnitine protects against cyclosporine-induced pancreatic and renal injury in rats   LUO Kang,JIN Ying-shun,PIAO Shang-guo,et al. Division of Nephrology & Dialysis Unit, Department of Internal Medicine,YanBian University Hospital,YanJi 133000,China

Corresponding author：LI Can, E-mail：lican@ybu.edu.cn

　　【Abstract】Objective To evaluate the beneficial effects of L-carnitine on pancreatic and renal injuries caused by cyclosporine A (CsA). Methods Rats were divided into vehicle (VH) group, vehicle+50 mg/(kg·d) L-carnitine (VH+L50) group, vehicle+200 mg/(kg·d) L-carnitine (VH+L200) group, CsA group, CsA+L-carnitine (CsA+L50) group and CsA+L-carnitine (CsA+L200) group.Pancreas and kidney function, the expression of light chain 3 (LC3-Ⅱ), tubulointerstitial fibrosis, TGF-β1, 8-hydroxy-2ˊ-deoxyguanosine(8-OHdG) were detected. Results CsA treatment caused diabetes (increased plasma glucose and HbA1c level, and decreased plasma insulin level,P<0.01), renal dysfunction (increased serum creatinine and blood urea nitrogen level,P<0.01), significant increase in the percentage of tubulointerstitial fibrosis, and this was accompanied by increase in 8-OHdG production, upregulation of TGF-β1 and LC3-Ⅱ expression (P<0.01). Concomitant administration of L-carnitine increased plasma insulin concentration and decreased levels of plasma glucose and HbA1c (P<0.05). In the kidney, L-carnitine induced dose-dependent improvement of renal function and fibrosis in parallel with suppression of TGF-β1 and 8-OHdG expression. Furthermore, L-carnitine at a high dose inhibited LC3-Ⅱ expression (P<0.05). Conclusion These findings suggest that L-carnitine has a protective effect against CsA-induced pancreatic and renal injuries.

　　【Key words】L-carnitine;Cyclosporine A (CsA);Transforming growth factor-β1 (TGF-β1);8-hydroxy-2ˊ-deoxyguanosine (8-OHdG);Autophagy