干旱区生态环境知识资源中心(Arid): 国产罗格列酮对实验性树鼩肝脂肪变性的保护作用

Arid

	国产罗格列酮对实验性树鼩肝脂肪变性的保护作用
其他题名	The protective effects of rosiglitazone on tree shrew’s fatty liver
	蒙碧辉 1; 梁世坤 1; 黄松 1; 冼苏 1; 舒昌达 2
来源期刊	中华消化杂志
ISSN	0254-1432
出版年	2003
卷号	23 期号:12 页码:718-722
中文摘要	目的探讨国产罗格列酮对高糖高脂喂养诱导树鼩肝脂肪变性干预治疗的效果。方法36只树鼩分为对照组8只（A组），喂常规鼠饲料。另28只喟高糖高脂饲料，并于22周将血糖≥11.1 mmol/L的19只动物再分为药物干预组8只（B组）和非干预组11只（C组）。B组以国产罗格列酮按每天5 mg/kg的剂量清晨一次性给药，用药7周。实验前、后检测体重（Wt）、空腹血糖（FBG）、血指4项[总胆固醇（TC），三酰甘油（TG），高密度脂蛋白胆固醇（HDL-C），低密度脂蛋白胆固醇（LDL-C）]、空腹血清胰岛素（FINS）和血清转氨酶水平。实验结束时剖腹取肝标本，光镜下观察肝脏形态学改变，以免疫组化法检测肝脏解偶联蛋白3（UCP3）和胰岛素受体beta（IR-beta）的表达水平，以计算机图像分析系统对UCP3、IR-beta表达作细胞阳性计数和面积密度及灰度分析。结果(1)血生化改变：B、C两组动物FBG均明显增高，实验结束时C组的血糖仍居高不下，同时血TC、TG增加值、FINS和自身稳定模型评估法胰岛素抵抗指数（HOMA-IR）也明显增高，而B组的FBG则显著下降，其他生化参数也均与对照组相似。(2)肝脏形态学：B、C两组动物均出现弥漫画性肝脂肪变性，脂肪变性的面积密度和肝细胞脂变率均在30%左右，两组差异均无显著性。实验结束时，B组肝脂肪变性显著改善，C组则进一步加重。(3)免疫组化分析：C组IR-beta表达明显强于A组（P＜0.01）；正常肝细胞不表达UCP3，C组肝细胞表达UCP3的面积密度和细胞阳性率均明显小于B组（P＜0.01）；肝肪脂变性面积密度与UCP3面积密度（r = -0.86, P = 0.001）和细胞阳性率（r = -0.79, p < 0.001）呈负相关。结论国产罗格列酮可能通过改善胰岛素抵抗、提高胰岛素敏感性、促进肝脏UCP3的表达，对实验性树鼩肝脂肪变性起防治作用。
英文摘要	Objective To investigate the effects of rosiglilazone on tree shrew’s fatty liver induced by high sugar and fat diet. Methods Thirty six tree shrews were assigned as the chow diet group (group A, 8 animals) and the high sugar-arid high fat-fed group (28 animals). The latter were fed alternately with the mix-food containing 40 % saccharu and 20% fat by one day interval. In the high sugar-and high fat-fed group, 19 animals (67.86% ), which had an increased FBG level equal to or more than 11.1 mmol/L 22 weeks after the diet, were divided into 2 subgroups: rosiglitazone-supplemented group (group B) , to which rosiglitazone was added at a dose of 5 mg·kg~(-1)·d~(-1) for seven weeks, and non-supplemented group (group C). Body weight, fasting serum insuiin(FINS) and blood lipid including total cholesterol (TC) , triglyceride (TG) , high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were examined dur-ing the experiment. Liver biopsies were carried out under general anaesthesia at 22 week and the end of the experiment in all animals. The samples of liver were fixed in 4% polymerisatum for 12 h, then through patho-logical routine processing. The expressions of uncoupling protein 3 (UCP3) and insulin receptor (IR) were an-alyzed by calculating the UCP3 and IR- expressing positive cells and by analyzing the area density of positive cells using computer-aided video system. Results Morphological alteration under light microscopy showed that all animals from both group B and C had a typical steatosis throughout the liver sections 22 week alter high sugar and high fat feeding. The area density of steatosis and the proportion of involved hepatocytes were approximately 30 % and reached higher degrees in group C (P<0.05) at 24 week, while those in group B re-duced markedly by more than 90% ( P < 0. 01 ) after administration of rosiglitazone. A smaller proportion of hepalocytes from group C (27. 6% + 4. 9% , P < 0. 01 ) was positive lor UCP3 by immunohistochemistry. compared with group P> (57.71 % 19.2% ). I he expression level of UCP3 prolein in liver was correlated re-versely with both the area density of hepatosteatosis ( r = - 0.86, P<0.01) and the proportion of stentosis cells( r = - 0.79, P<0.01). In group C the expression level of IR-beta in the liver was higher than that of controls ( P < 0. 05 ), and there was an increased blood level of IV in group C compared with its baseline ( P - 0.33) as well as with group B (P =0.01) and pure increased values of TG compared with group B (P<0. 05) at the end of the trial. As for group B, no significant changes were observed in the values of blood lipids. FBG increased progressively with time in group B and C, from 13 week after the experiment to 22 week of peak levels (FBG≥11.1 mmol/L). In the end of the experiment (29 week) , group H had a lower blood glu-cose level than group C ( P<0.05), while the values of FBG were significantly higher in group C than in both group A and B (all P< 0. 05). Group (’ also had a greater value of FINS and more homocestasis model assess-ment of insulin resistance (HOMA-IR) than group A and B (all P<0.05), while there were no significant differences of FINS and HOMA-IR between group B and group A (all P >0. 05) .Conclusion Increased ex-pression of liver for IR-\|3 in tree shrews on a high sugar and high fat diet indicates that insulin signaling may have a role in the development of hepatostealosis.
中文关键词	脂肪肝 ; 罗格列酮 ; 解偶联蛋白 ; 胰岛素抵抗 ; 树鼩
英文关键词	fatty liver rosiglitazone uncoupling protein insulin resistance tree shrew
语种	中文
国家	中国
收录类别	CSCD
WOS类目	MEDICINE GENERAL INTERNAL
WOS研究方向	General & Internal Medicine
CSCD记录号	CSCD:1244689
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/204734
作者单位	1.广西医科大学第一附属医院内分泌科, 南宁, 广西 530021, 中国; 2.重庆医科大学第一医院内分泌科
推荐引用方式 GB/T 7714	蒙碧辉,梁世坤,黄松,等. 国产罗格列酮对实验性树鼩肝脂肪变性的保护作用[J],2003,23(12):718-722.
APA	蒙碧辉,梁世坤,黄松,冼苏,&舒昌达.(2003).国产罗格列酮对实验性树鼩肝脂肪变性的保护作用.中华消化杂志,23(12),718-722.
MLA	蒙碧辉,et al."国产罗格列酮对实验性树鼩肝脂肪变性的保护作用".中华消化杂志 23.12(2003):718-722.