动物造模,室性心律失常 z-bio 2023-02-02 971

　　Objective To investigate the loss of myeloid differentiation protein 1 (MD1) by activating the Toll-like receptor 4 (TLR4) / myeloid differentiation factor (MyD88) signaling pathway to increase the susceptibility of obese mice to ventricular arrhythmia.

　　Method 16 MD1 knockout mice and 16 male WT mice were grouped into WT normal group, MD1-ko-normal group, WT high-fat group, MD1-ko-high-fat group. The mice in the WT high-fat group and MD1-ko-high-fat group were fed with high-fat food (60% fat) for 20 weeks, and the WT normal group and MD1-ko-normal group were fed with normal diet (10% fat). Measure the mouse's body weight (BW), blood sugar level, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels, and the ratio of HW/BW. Measure RR interval, PR interval, QRS duration, QTc interval, LVEDd, LVEDs, LVFS and LVEF by ECG and echocardiogram. Western blot was used to analyze the protein levels of TLR4, MyD88, P-CAMKII, CollagenI, CollagenIII and TGF-β1. HE staining and PSR staining were used to observe myocardial hypertrophy and fibrosis in mice.

　　Results The body index, blood glucose level, total cholesterol, triglycerides, low-density lipoprotein cholesterol, QTc interval, LVEDd, LVEDs, LVFS, and LVEF in the MD1-ko-high-fat group were significantly higher than those in the WT high-fat group (all P<0.05); MD1-ko-high-fat group's action point time course (APD20, APD50, APD90) was significantly higher than WT high-fat group (P<0.05); MD1-ko-high-fat group APD alternate The threshold was significantly higher than the WT high-fat group (P<0.05); the proportion of arrhythmia in the MD1-ko-high-fat group was significantly higher than the WT high-fat group (P<0.05); TLR4 in the MD1-ko-high-fat group , MyD88 and P-CAMKII protein expression was significantly higher than that of WT high-fat group (all P<0.05); MD1-ko-high-fat group HW/BW ratio (7.59±0.78) was significantly higher than WT high-fat group Lipid group (6.07±0.58) (P<0.05). The cross-sectional area of myocardial cells in the MD1-ko-high-fat group (381.23±35.76) μm2 was significantly higher than that of the WT high-fat group (190.15±25.23) μm2 (P<0.05); MD1 CollagenI, CollagenIII and TGF-β1 proteins in the -ko-high-fat group were significantly higher than those in the WT high-fat group (P<0.05).

　　Conclusion The lack of MD1 increases the susceptibility of high-fat diet-induced arrhythmia, mainly due to the enhanced activation of the TLR4 / MyD88 signaling pathway, leading to left ventricular hypertrophy and fibrosis, and increasing the expression of TLR4 / MyD88 signaling pathway-related proteins.