左卡尼汀对环孢素A所致胰腺和肾脏损伤的保护作用  

L-carnitine treatment protects against cyclosporine-induced pancreatic and renal injury in rats

作　　者：罗康[1] 金英顺[1] 朴尚国 方梅荣 刘金莲[1] 邹洪斌[2] 高弼虎[3] 项莹 金健[1] 李灿[1] 

机构地区：[1]延边大学附属医院肾内科,延吉133000 [2]吉林大学第一医院肾内科 [3]大连大学附属中山医院肾内科

出　　处：《中国糖尿病杂志》2014年第2期161-165,共5页Chinese Journal of Diabetes

基　　金：国家自然科学基金(81160092)

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、CsA组、CsA+左卡尼汀低剂量治疗(CsA+L50)组和CsA十左卡尼汀高剂量治疗(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Scr和BUN升高、TIF增加(P<0.01),该变化伴随TGF-β1、8-OHdG和LC3-Ⅱ表达增加。左卡尼汀治疗对各指标均有效,LC3-Ⅱ表达仅在左卡尼汀高剂量治疗下减少(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。Objective To evaluate the beneficial effects of L-camitine 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-2′-deoxyguanosine （8-OHdG） were detected. Results CsA treatment caused diabetes （increased plasma glucose and HbA1 c 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 that 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 HbA1 c （P〈0. 01）. 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.

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 

分 类 号：R96[医药卫生—药理学]