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脂联素对大鼠慢性间歇性低氧所致心肌重塑的影响
Effects of adiponectin on myocardiac remodeling induced by chronic intermittent hypoxia in Wistar rats
【摘要】 目的 探讨慢性间歇性低氧(chronic intermittent hypoxia,CIH)对心肌重塑的影响及脂联素(adiponectin,Ad)的干预作用。方法 将45只Wistar大鼠随机分为3组:正常对照组(NC),CIH组和CIH+Ad组。CIH 35d后,使用马松染色分析方法检测左室纤维化程度及使用Western blot方法来衡量Ⅰ型胶原蛋白、Ⅲ型胶原蛋白和TGF-β/smad2/3通路蛋白的表达。通过RT-PCR方法来研究基质金属蛋白酶-2(MMP2)/基质金属蛋白酶的组织抑制剂-2(TIMP-2)的mRNA表达比值情况。结果 慢性间歇性低氧处理后,CIH组左心室的纤维化程度显著高于NC组和CIH+Ad组(P<0.05),但NC组和CIH+Ad组之间差异具有统计学意义(P<0.05)。CIH组Ⅰ型胶原蛋白和Ⅲ型胶原蛋白和MMP2/TIMP-2的mRNA比值表达最高,NC组表达最低,CIH+Ad组居中,3组之间均差异具有统计学意义(P<0.05)。TGF-β/smad通路蛋白在CIH组中表达显著高于NC组和CIH组(P<0.05),且NC组和CIH+Ad组差异具有统计学意义(P<0.05)。结论 慢性间歇性低氧可引起左室重构,而Ad可能通过抑制TGF-β/smad2/3通路改善此损害。
【Abstract】 Objective To investigate the effects of chronic intermittent hypoxia(CIH) on myocardiac remodeling and intervention role of adiponectin(Ad) in the process.Methods A total of 45 Wistar rats were randomly divided into 3 groups:normal control(NC)group,CIH group and CIH + Ad group(10 μg Ad injection through caudal vein twice per week,for 5 weeks).After 35 days’ CIH exposure(in a chamber with 60 s nitrogen infusion to reduce the oxygen concentration to 5%followed by another 60 s oxygen infusion to increase the concentration to 20%for totally 8 h of each day),Masson analysis was used to detect the left ventricular fibrosis,and Western blot was used to measure the protein expression of collagen Ⅰ,collagen Ⅱ and pathway proteins TGF-β/smad2/3.RT-PCR was used to study the expression of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-2(TIMP-2).Results After CIH exposure,the left ventricular fibrosis was significantly more severe in CIH group than in NC group and CIH + Ad group(P<0.05),and there was statistical difference between the 2 latter groups(P<0.05).In addition,the protein expression of collagen Ⅰ and collagen Ⅲ and the mRNA expression of MMP-2 and TIMP-2 were the highest in CIH group,the lowest in NC group,and CIH + Ad group in the middle.There was a significant difference among 3 groups(all P < 0.05).The pathway proteins TGF-β/smad2/3 were most significantly expressed in CIH group(P < 0.05),but there was still significant difference in their expression between NC group and CIH + Ad group(P < 0.05).Conclusion CIH may cause may left ventricular remodeling,while Ad supplement may ameliorate the impairment via inhibiting TGF-p/smad2/3 pathway.
- 【文献出处】 中华老年多器官疾病杂志 ,Chinese Journal of Multiple Organ Diseases in the Elderly , 编辑部邮箱 ,2014年10期
- 【分类号】R766