肾衰养真胶囊对慢性肾衰竭营养不良大鼠Leptin-下丘脑NPY、POMC轴的影响

目的观察肾衰养真胶囊对慢性肾衰竭(chronic renal failure,CRF)营养不良大鼠瘦素(leptin,LP)-下丘脑神经肽Y(neusropeptide Y,NPY)及阿片-促黑素细胞皮质素原(proopiomelanocortin,POMC)轴的影响。方法 42只SD雄性SPF级大鼠,随机选取正常组8只,其余大鼠采用5/6肾切除同时予4%酪蛋白饮食制作CRF营养不良大鼠模型,观察其营养不良发生时间,随机分为肾衰养真胶囊组(SSYZC组)11只、复方α-酮酸组(对照组)11只、模型组12只。治疗4周后,检测肌酐(serum creatinine,Scr)、尿素氮(blood urea nitrogen,BUN)、24小时尿蛋白(24 hour urine protein,24 h Upr)、白蛋白(albumin,ALB)、血红蛋白(haemoglobin,Hb)、胰岛素样生长因子-1(type-1 insulin like growth factor,IGF-1)、总胆固醇(total cholesterol,TC)、甘油三脂(triglyeride,TG),动态观察摄食量及体重变化,应用放射免疫法检测血浆瘦素(leptin,LP)、下丘脑神经肽Y(neusopeptide Y,NPY)和RT-PCR法检测下丘脑OB-Rb mRNA、NPYmRNA和POMCmRNA表达水平。结果 CRF大鼠在术后10周末出现营养不良,SSYZC组大鼠摄食量、体重显著增高(P0.05),肾功能及营养状况明显改善(P0.05),肾衰养真胶囊可降低血浆LP、NPY水平(P0.05);可上调下丘脑NPY mRNA表达(P0.01)及下调OB-Rb mRNA、POMC mRNA表达(P0.01)。结论肾衰养真胶囊可能通过上调下丘脑NPY mRNA表达及下调OB-Rb mRNA、POMC mRNA表达,从而促进大鼠摄食,改善CRF营养不良。

Effects of Shenshuai Yangzhen Capsule on Hypothalamic Leptin-Neuropeptide and Proopiomelanocortin Axes in Chronic Renal Failure Rats with Malnutrition

Objective To investigate the effect of Shenshuai Yangzhen Capsule（SYC） on hypothalamic leptin-neuropeptide Y（NPY） and proopiomelanocortin（POMC） axes in chronic renal failure（CRF） rats with malnutrition（MN）.Methods Forty-two male SD rats of SPF grade were established into CRF-MN model by 5/6 nephrectomy and 4%casein diet,the happening time of MN in them was recorded.Rats successfully modeled were randomized into three groups,11 rats in Group A treated with SYC,11 in group B treated with compositeα-keto acid and 12 in Group C was untreated.Besides,a normal control group was set up with 8 healthy rats.After being treated for 4 weeks,the renal function related indices,including serum creatinine（Scr）,blood urea nitrogen （BUN）,24 hour urine protein（24 h Upro）,albumin（ALB）,haemoglobin（Hb） insulin like growth factor-1 （IGF-1）,total cholesterol（TC） and triglyeride（TG） were measured,and body weight,food intake in rats were observed dynamically,blood leptin and NPY level in rats were determined by radioimmunoassay;mRNA expressions of OB-Rb,NPY and POMC in hypothalamus were detected with RT-PCR.Results CRF rats revealed MN at the end of 10th week after modeling.Compared with Group C,the condition of MN in Group A was significantly improved,showing increase of food intake and body weight（P0.05）,marked improvement of renal function （P0.05）,decrease of LP and NPY levels in plasma（P0.05）,as well as up-regulated NPY mRNA expression and down-regulated mRNA expressions of OB-Rb and POMC in hypothalamus（P0.01 ）. Conclusion SYC can improve the malnutrition condition in rats with CRF,which is possibly by way of depressing OB-Rb and POMC mRNA expression and upgrading NPY mRNA expression in hypothalamus.