高脂高糖饮食诱导胰岛素抵抗大鼠心脏功能和心肌Ⅰ型胶原改变及替米沙坦干预的影响

目的 探讨高脂高糖饮食诱导胰岛素抵抗大鼠心脏功能和心肌Ⅰ型胶原改变及替米沙坦干预后对其影响。方法 27只Wistar大鼠随机分为正常对照组(n=9只)、高脂高糖饮食组（n=18只），高脂高糖饮食干预12周后确定胰岛素抵抗模型建立，将高脂高糖饮食组随机分为高脂高糖组（n=9只）和替米沙坦组（n=9只）。饮食干预34周后颈动脉插管测左室舒张末内压（LVEDP）、左室收缩压（LVSP）和左室内压最大下降速率（-dP/dtmax）。ELISA方法检测血浆中心肌Ⅰ型胶原代谢标志物Ⅰ型前胶原末端的前肽序列(PICP)和Ⅰ型胶原吡啶交联终肽(ICTP)的含量。心肌组织Masson染色进行心肌间质胶原定量分析。结果 与正常对照组比较，高脂高糖组大鼠LVEDP上升，-dP/dtmax下降(P<0.01)，血浆PICP含量及PICP/ICTP升高(P<0.01)，左室心肌胶原容积分数增高(P<0.01)。与高脂高糖组大鼠比较，替米沙坦组大鼠LVSP、LVEDP均显著下降(P<0.01)，-dP/dtmax升高(P<0.05)；血浆PICP含量、PICP/ICTP降低(P<0.05)。左室心肌胶原容积分数含量显著下降(P<0.01)。左室心肌组织胶原含量与胰岛素抵抗指数呈显著正相关(R=0.634,P<0.01)，与-dp/dtmax呈显著负相关(P<0.01)。结论 胰岛素抵抗大鼠心肌Ⅰ型胶原合成增加，心肌间质胶原沉积增加，心脏舒张功能下降；替米沙坦可改善胰岛素抵抗，减少胰岛素抵抗大鼠心肌Ⅰ型胶原的合成，减少心肌间质胶原沉积，改善心脏舒张功能。

Changes of cardiac function in high-fat,high-glucose diet-induced insulin resistance in rats and telmisartan intervention study

AIM To explore cardiac functions and myocardial collagen type I in diet-induced insulin-resistant rats and the effect of telmisartan on cardiac diastolic functions in diet-induced insulin-resistant rats. METHODSTwenty-seven Wistar rats were randomized into control group, high-fat high-glucose group and telmisartan treatment group. At the end of the study, left ventricular internal pressure and -dp/dtmax were detected by carotid artery intubation. Cardiac fibrosis was observed using Masson cardiac staining and collagen volume fraction (CVF) was measured. ELISA method was used to detect the concentration of plasma PICP and ICTP. RESULTSCompared with those in control group, left ventricular end diastolic pressure in high-fat high-glucose group was significantly higher, -dP/dtmax decreased significantly, plasma PICP levels and the ratio of PICP/ICTP significantly increased and cardiac collagen volume fraction was significantly higher. After a 22-week telmisartan intervention, LVEDP and LVSP significantly decreased and -dP/dtmax significantly increased. The level of PICP and PICP/ICTP significantly decreased and left ventricular myocardial tissue collagen volume fraction content decreased. Correlation analysis showed that cardiac collagen volume fraction in insulin-resistant group was positively correlated with insulin resistance index and negatively correlated with -dp/dtmax (P<0.01). CONCLUSIONInsulin resistance promotes myocardial type I collagen synthesis, leading to increased myocardial collagen deposition and decreased cardiac diastolic function. Telmisartan may improve diastolic function partly by improving insulin resistance and reducing the deposition of myocardial collagen type I.