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.