1型糖尿病对血脂代谢及肾和心脏组织结构的影响

Lipid abnormalities,renal and cardiac histology changes in rabbits with type 1 diabetes

目的探讨1型糖尿病对血脂代谢及肾和心脏组织结构的影响。方法随机选取新西兰大白兔36只,分为糖尿病组(DM,20只)和对照组(NC,16只),两次四氧嘧啶(ALX,80mg/kg)耳缘静脉注射复制1型糖尿病模型,期间进行血糖控制。饲养4周,观察兔一般情况,4周末采血检测血脂变化,包括TG、TC、LDL-C、HDL-C水平、载脂蛋白(Apo)A1、ApoB100、ApoE,处死兔后膀胱穿刺抽取尿液检测尿常规和尿蛋白定量,分离心脏和肾脏进行病理组织检查。结果实验造模成功率为55%,死亡率为40%。DM组TC、HDL-C、LDL-C水平显著高于NC组(P<0.01),其中TC、TG、LDL-C水平较NC组分别升高97%,48%,130%。DM组TC/HDL-C,LDL-C/HDL-C水平高于NC组(P<0.01),但TG/HDL-C水平低于NC组;两组ApoB 100、ApoA1/ApoB100、ApoE差异无统计学意义(均P>0.05)。DM组尿蛋白定量较NC组升高。DM组心肌病理检查出现轻度-中-重度不同程度的心内膜下脂肪变性和沉积,肾脏病理检查提示肾小球血管袢分叶数量增加,基底膜及系膜基质增生,肾小球体积缩小,部分出现脂肪变替代,肾小管出现不同程度范围变性甚至坏死,腔内可见钙盐沉积。结论 1型糖尿病可导致脂质代谢紊乱,引起心脏和肾脏病变,需行积极降脂治疗。

Objective To investigate the changes of lipid metabolism, renal and cardiac histology in type 1 diabetes. Methods Thirty six New Zealand rabbits were randomly divided into diabetes mel itus group （DM, n=20） and normal control group （NC, n=16）. Type 1 diabetes was induced by injection of Al oxan（80mg/kg） twice via ear marginal venous, the same vol-ume of normal saline was injected in NC group. The general conditions, body weight, food and water intake were observed for 4 weeks after injection; blood total cholesterol （TC）, triglyceride （TG）, low density lipoprotein cholesterol （LDL- C）, high density lipoprotein cholesterol（HDL- C）, apolipoprotein A（apoA）, apolipoprotein B（apoB） and apolipoprotein E（apoE） levels were deter-mined, and routine urine test, urine protein were measured by the end of the experiment; and histopathological examination of heart and renal were performed. Results The TC, HDL- C, LDL- C levels and TC/HDL- C, LDL- C/HDL- C in DM group were significantly higher than those in NC group （P〈0.01）, but there was no significant difference in ApoB100 levels and ApoA1/ApoB100 between two groups. Compared to NC group the levels of TC, TG, LDL- C in DM group were elevated by 97%, 48%and 130%, respectively;there were no statistical differences in the ratio of TG/HDL- C and ApoE level between two groups. The urine protein level in DM group was higher than that in NC group. Histopathological examination showed that there were cel edema, disordered arrangement of myocardial fibers, interstitial enlargement, mild- moderate- severe lipid accumulation and fatty degeneration under the epicardium in the heart of DM group. Basement membrane and mesangial matrix proliferation, glomerular volume shrinking and glomerular fatty degeneration, mild- moderate- severe tubular degeneration and necrosis, cal-cium salt deposits were observed in the cavity of distal convoluted tubule in diabetic kidney. Conclusion Type 1 diabetes may result in dyslipidemia and heart and kidney dysfunction, which are associated with pathogenesis of diabetic nephropathy and cardiomyopathy.