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 inducedbychronic intermittent hypoxiain Wistar rats

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。

ObjectiveTo 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 Wistarrats were randomly divided into3 groups： normal control （NC） group, CIH group and CIH＋Ad group （10μg 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 theoxygen concentration to 5% followed by another 60 s oxygen infusion to increase theconcentration 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 collagenⅠ, collagenⅢ 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 groupand 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 collagenⅠ and collagenⅢ 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 CIHmay cause may left ventricular remodeling, while Ad supplementmay ameliorate the impairmentvia inhibiting TGF-β/smad2/3 pathway.