平滑肌特异性PGC-1α转基因小鼠抗急性结肠炎的效应及其机制  

Smooth muscle-specific overexpression of PGC-1α protects mice from acute colitis

作　　者：刘一笑[1] 陈腾飞[2] 王梦雨[1] 崔鑫[1] 唐寅[1] 黄薇[1] 张玲[1] 刘占举[2] 刘国庆[1] 

机构地区：[1]北京大学医学部心血管所教育部分子心血管学重点实验室,北京市100191 [2]同济大学附属第十人民医院胃肠科,上海市200072

出　　处：《世界华人消化杂志》2012年第20期1824-1831,共8页World Chinese Journal of Digestology

摘　　要：目的:探讨平滑肌特异性过表达过氧化物酶增殖体激活受体辅助激活因子1α(SMC-PGC-1α)对葡聚糖硫酸钠(dextran sulfate sod-ium,DSS)诱导的小鼠急性结肠炎的影响.方法:按照SMC-PGC-1α转基因阴性/阳性(non-Tg/Tg)及诱导与否分为4组,每组10-13只.诱导组给予3% DSS自由饮用7d诱导急性结肠炎,对照组则给予正常饮用水.通过疾病活动指数(disease activity index,DAI)评估及结肠组织病理学评分(histopathological score,HPS)来明确SMC-PGC-1α过表达对DSS诱导的小鼠急性结肠炎的影响,并通过对结肠炎相关基因mRNA表达水平的检测来研究SMC-PGC-1抗结肠炎的作用机制.结果:诱导组相较于对照组:(1)体质量减轻明显(P<0.01);(2)DAI明显升高(P<0.01);(3)结肠长度明显缩短(non-Tg组中5.0cm+0.3cm vs 7.8cm+0.2cm;Tg组中4.9cm+0.1cm vs 8.0cm+0.3cm,P<0.01);(4)HSP明显加重(non-Tg组中9.6+1.2 vs 1.2+0.4;Tg组中5.0+0.8 vs 1.2+0.6,P<0.01).说明肠炎造模成功.诱导组中,Tg组相较于non-Tg组:(1)DAI明显降低(P<0.01);(2)HPS明显减轻(5.0+0.8 vs 9.6+1.2,5.0+0.8 vs 1.2+0.6,P<0.01);(3)TNF基因表达水平降低(0.24+0.07vs0.45+0.10,P<0.05);(4)PPARγ基因表达水平增高(0.98+0.15 vs 0.41+0.07,P<0.05).结论:SMC-PGC-1α过表达可能通过激活PPARγ,降低炎症因子TNFα的表达,从而在DSS诱导的急性结肠炎中对结肠起到保护作用.AIM： To investigate the effect of smooth muscle- specific overexpression of peroxidase prolif- erator-activated receptor gamma coactivator- 1α （PGC-α） on dextran sulfate sodium （DSS）- induced acute colitis in mice.METHODS： Two-month-old male mice were divided into four groups according to geno- type （non-Tg/Tg） and treatment （H20/DSS）, 10-13 mice for each group. Mice were adminis- tered with 3% DSS in drinking water for 7 days （＋DSS） to induce inflammatory bowel disease （IBD）. Control groups were given normal drink- ing water （＋H20）. At the end of the study, the symptoms and pathological changes were evalu- ated using disease activity index （DAI） and histopathological score （HPS） of acute colitis, respectively. The mRNA levels of inflammatory cytokines in the colon were determined. RESULTS： Compared to control groups, DSS- treated groups had significantly decreased body weight （both P 〈 0.01）, increased DAI （both P 〈 0.01） and HPS （9.6 ＋ 1.2 vs 1.2 ＋ 0.4; 5.0 ＋ 0.8 vs 1.2 ＋ 0.6, in non-Tg and Tg groups, respectively, both P 〈 0.01）, and significantly shorter colon （5.0 cm ＋ 0.3 cm vs 7.8 cm ＋ 0.2 cm; 4.9 cm ＋ 0.1 cm vs 8.0 cm ＋ 0.3 cm, in non-Tg and Tg groups, respectively, both P 〈 0.01）. Compared to the DSS-treated non-Tg group, the treated Tg group had significantly decreased DAI （P 〈 0.01）, HPS （5.0 ＋ 0.8 vs 9.6 ＋ 1.2, P 〈 0.01） and tumor necro- sis factor ct （TNFc0 mRNA level （0.24 ＋ 0.07 vs 0.45 ＋ 0.10, P 〈 0.05）, and increased peroxidase proliferator-activated receptor ~, （PPARy） mRNA level （0.98 ＋ 0.15 vs 0.41 ＋ 0.07, P 〈 0.05）. CONCLUSION： Smooth muscle-specific over- expression of PGC-1R protects against DSS-in- duced acute colitis by reducing the expression of inflammatory factor TNF~, which might result from the activation of PPARy.

关 键 词：过氧化物酶增殖体激活受体辅助激活因子1α 葡聚糖硫酸钠 炎性肠病 

分 类 号：R574.62[医药卫生—消化系统]