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目的探讨Connexin43(Cx43)在野百合碱(MCT)致右心衰竭幼鼠中的变化及卡托普利和坎地沙坦的干预作用。方法 50只SD幼鼠腹腔注射MCT诱发肺动脉高压(PAH),随机分为心衰4周组(E1组)、心衰6周组(E2组)、卡托普利组(C1组)、坎地沙坦组(C2组)和二药联合组(C3组)。另20只幼鼠腹腔注射9g.L-1盐水作为对照,分为正常对照4周组(N1组)和正常对照6周组(N2组)。测定每组存活幼鼠的血流动力学和相关生理指标,采用ELISA法检测其血清Cx43水平,免疫组织化学法和RT-PCR法测定其右心室心肌组织Cx43和Cx43mRNA的表达。结果 E1组与N1组比较,右心室肥厚指数、中心静脉压(CVP)、右心室收缩压(RVSP)显著升高,右心室压最大上升速率(RVdp/dt)显著降低,右心室心肌细胞排列紊乱、肌浆溶解,并可见空泡变性,右心衰竭模型成功。E1组血清Cx43水平、右心室心肌组织Cx43和Cx43mRNA均较N1组降低。E2组与N2组比较,CVP、RVSP显著增高,RVdp/dt显著降低,血清Cx43水平、右心室心肌组织Cx43蛋白和Cx43mRNA均降低。E2组与E1组比较,右心室肥厚指数、CVP、RVSP持续增高,RVdp/dt持续降低,E2组血清Cx43、右心肌组织Cx43蛋白和Cx43mRNA进一步降低。C1组、C2组与E2组比较,血流动力学改善,右心室肥厚减轻,血清Cx43水平、右心肌组织Cx43蛋白和Cx43mRNA均增高。C1组、C2组分别与C3组比较,血流动力学、血清Cx43水平、右心室心肌组织Cx43蛋白和Cx43mRNA表达比较差异均无统计学意义。结论 PAH致右心衰竭时,Cx43参与心力衰竭的发生发展,随着心力衰竭的加重,其表达进一步降低;Cx43在幼鼠血清、右心室心肌组织中的水平具有一致性;卡托普利或坎地沙坦可能通过促进Cx43的表达缓解压力负荷性右心衰竭,二者比较无明显差异,联合用药并不能提高疗效。
Objective To investigate the changes of Connexin43 (Cx43) in immature rats induced by monocrotaline (MCT) and the effects of captopril and candesartan. Methods Fifty male SD rats were intraperitoneally injected with MCT to induce pulmonary hypertension (PAH), and were randomly divided into four groups: heart failure group (E1 group), heart failure group (E2 group), captopril group (group C1) Desi Tan group (C2 group) and two drug combination group (C3 group). Another 20 mice were intraperitoneally injected with 9g.L-1 saline as a control, and were divided into normal control 4 weeks group (N1 group) and normal control 6 weeks group (N2 group). Serum Cx43 levels were measured by ELISA. The expression of Cx43 and Cx43 mRNA in right ventricular myocardium was detected by immunohistochemistry and RT-PCR. Results Compared with N1 group, right ventricular hypertrophy index, central venous pressure (CVP) and right ventricular systolic pressure (RVSP) increased significantly and RVdp / dt decreased significantly Disorders, sarcoplasmic lysis, and visible vacuolar degeneration, right heart failure model was successful. Serum levels of Cx43 in E1 group and Cx43 mRNA in right ventricular myocardium were lower than those in N1 group. Compared with N2 group, the CVP and RVSP were significantly increased in E2 group and RVdp / dt, while the levels of Cx43 and Cx43 mRNA and Cx43 in right ventricular myocardium were decreased. Compared with the E1 group, the right ventricular hypertrophy index, CVP, RVSP increased continuously and the RVdp / dt decreased continuously in the E2 group. The Cx43, Cx43 and Cx43 mRNA in the E2 group decreased further. C1 group, C2 group and E2 group, hemodynamic improvement, reduce right ventricular hypertrophy, serum Cx43 level, right Cx43 protein and Cx43 mRNA were increased. There was no significant difference in hemodynamics, serum Cx43 level, Cx43 protein and Cx43 mRNA expression in C1 and C2 groups compared with C3 group respectively. Conclusions Cx43 is involved in the development of heart failure induced by PAH. The expression of Cx43 is further decreased with the increase of heart failure. The levels of Cx43 in the serum and right ventricular myocardium of young rats are consistent. Captopril or Candesartan may relieve stress-loaded right heart failure by promoting the expression of Cx43, there is no significant difference between the two, and the combination therapy can not improve the curative effect.