硫化氢对代谢综合症小鼠心脏的保护作用

Hydrogen sulfide protects heart against injury in MS

目的观察代谢综合症小鼠内源性硫化氢系统的变化及其对心脏损伤的作用。方法按空腹血糖水平将KK/Upj-Ay/J小鼠(7～9W)分层随机分为模型组(MS),MS+NaHS组和MS+PPG组,C57BL/6J小鼠(7～9W)为正常对照组(CON)。One Touch血糖仪测定各组空腹血糖,全自动生化分析仪测血脂,比色法测血浆H_2S浓度,心肌H_2S含量和心肌CSE(胱硫醚-γ-裂解酶)活性,RT-PCR法测心肌CSEmRNA表达水平,HE染色测心室壁厚度,心肌细胞直径,荧光染色测心肌中vWF(血管性假血友病因子)和SMA(平滑肌肌动蛋白)阳性血管数目变化。结果KK/Upj-Ay/J小鼠的空腹血糖、血脂和肥胖指数比CON组均显著升高(P<0.05)。与CON组相比,MS组血浆中H_2S浓度,心肌H_2S合成酶CSE的活性和CSEmRNA的表达均显著降低(P<0.01,P<0.01,P<0.05)。与CON组相比,MS组心室壁厚度有所增加;心肌细胞直径显著增加(P<0.05);vWF和SMA阳性血管数目显著减少(P<0.01)。与MS组相比,MS+NaHS组心室壁厚度有所减小,心肌细胞直径显著减小(P<0.05),vWF和SMA阳性血管数目显著增加(P<0.01);MS+PPG组心室壁厚度有所增加,心肌细胞直径显著增加(P<0.05),SMA阳性血管数目显著减少(P<0.01)。结论MS小鼠体内H_2S/CSE体系下调导致心脏形态及功能的损伤性变化,上调该系统是治疗代谢综合症心脏损伤的潜在靶点。

Objective To explore the changes of hydrogen sulfide/cystathionine γ -lyase （H2S/ CSE） system in mouses with MS and the effect of the H2S/CSE system on hear in mouser. Methods KK/ Upj-Ay/j mouse（7-9W） were randomly divided into three groups according to fasting blood sugar （FBG）： the Metabolic system （MS） group, the MS ＋ NariS（ H2S donor） group, the MS ＋ ＋ DL-propargylglycine （PPG） group. The control group was C57BL/6J mouse（7-9W）. Four weeks later, the body weight （BW）, fasting blood sugar （FBG）, cholesterin （TC） , triglyeeride （TG） , high density lipoprotein （ HDL）, low density lipoprotein （LDL） , the H2 S level in plasma and myocardium , the activity and transcriptional level of CSE mRNA in heart, ventricle thickness, cardiomyocyte mean diameter, amount of vWF-positive vessels and SMA-positive vessels in each group were measured. Results The BW, abdomen circumference, FBG, TC, TG, HDL, LDL of KK/Upj-Ay/j were all higher than those of control group（P 〈0. 05）. The H2S concentration in plasma, the producing rate of H2S in myocardium and the expression of CSEmRNA was less than those of CON group（P〈 0. 01, P〈 0. 01,P〈 0. 05）. The ventricle thickness in MS was thicker than those of CON group, in MS ＋ H2S was thiner than those of MS group ,in MS ＋ PPG was thicker than those of MS group（ all P 〉0.05 ）. The myocardial cells mean diameter in MS was bigger than those of CON group, in MS ＋ H2 S was smaller than those of MS group, in MS ＋ PPG was bigger than those of MS group （ all P 〈 0. 05 ）. The Amount of vWF-positive and SMA- positive vessels in MS group were lesser than those of CON （P 〈 0. 01 ） ,while in MS ＋ H2S group were more than those of MS group（P 〈0. 01 ）. The Amount of vWF- positive vessels in MS ＋ PPG group was similar to those of MS group , while the SMA-positive vessels in MS ＋ PPG group were lesser than those of MS group（P 〈 0.01 ）. ConclusionThe H2S/CSE system is down-regulated in mouse with MS and is a major factor in the cardial injury. Exogenous H2S provides a new way for interfering with the progression of MS.