高脂饮食诱导胰岛素抵抗大鼠心脏功能和心肌Ⅰ型胶原的改变及替米沙坦的作用
Changes of cardiac function of high fat diet-induced insulin resistance rat and telmisartan intervention

摘要：目的 探讨高脂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)、高脂饮食组(n=18只)。高脂饮食干预12周后确定胰岛素抵抗模型建立，将高脂饮食组大鼠随机分为高脂组(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)、左室内压最大上升速率(+dP/dtmax)及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)、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，高脂组大鼠左室舒张末压上升，-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)。与高脂组大鼠比较，替米沙坦组大鼠左心室收缩压、左心室舒张末压下降(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下降(P<0.01)。左室心肌组织胶原含量与胰岛素抵抗指数呈正相关(P<0.01)，与-dp/dtmax呈负相关(P<0.01)。结论 胰岛素抵抗可通过促进心肌Ⅰ型胶原合成，增加心肌胶原沉积，导致心脏舒张功能下降；替米沙坦可通过改善胰岛素抵抗，减少心肌胶原沉积进而改善心脏舒张功能。
ABSTRACT: Objective To explore cardiac function and myocardial collagen type I in diet-induced insulin-resistant rats and the effect of telmisartan on cardiac diastolic function in diet-induced insulin-resistant rats. Methods We randomized 27 Wistar rats into control group (n=9), high-fat group (n=9), and telmisartan treatment group (n=9). At the end of the study, left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP) of the rats and ±dp/dt were detected by carotid artery intubation. Masson cardiac staining was used to observe cardiac fibrosis, and collagen volume fraction (CVF) was measured. ELISA method was used to detect the concentration of plasma PICP and ICTP. Results Compared with the control group, in high-fat group LVEDP was significantly higher and -dP/dtmax decreased significantly (P<0.01); the plasma PICP level and the ratio of PICP/ICTP were significantly increased (P<0.01), cardiac collagen volume fraction was significantly higher (P<0.01). After 22 weeks’ telmisartan intervention, compared with the high-fat group, LVEDP and LVSP were significantly decreased (P<0.01), but -dP/dtmax significantly increased (P<0.05). The level of the plasma PICP and PICP/ICTP were significantly decreased (P<0.05); left ventricular myocardial tissue collagen volume fraction content was decreased (P<0.01). The correlation analysis showed that cardiac collagen volume fraction in insulin-resistant group was positively correlated with insulin resistance index but negatively correlated with -dp/dtmax (P<0.01). Conclusion Insulin resistance promoted the synthesis of myocardial type I collagen, 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