动物造模 z-bio 2022-02-14 483

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

　　Methods 16 MD1 knockout mice and 16 male WT mice were divided into groups, namely WT normal group, MD1-ko-normal group, WT high-fat group, and MD1-ko-high-fat group. WT high-fat group and MD1-ko-high-fat group mice were fed high-fat chow (containing 60% fat) for 20 weeks, and WT normal group and MD1-ko-normal group were fed normal chow (containing 10% fat) for 20 weeks. Body weight (BW), blood glucose values, total cholesterol, triglyceride and LDL cholesterol levels, and HW/BW ratios were measured in mice. RR interval, PR interval, QRS duration, QTc interval, LVEDd, LVEDs, LVFS, and LVEF were measured by ECG and echocardiography. The protein levels of TLR4, MyD88, P-CAMKII, CollagenI, CollagenIII and TGF-β1 were analyzed by Western blot assay. Murine cardiac hypertrophy and fibrosis were observed by HE staining and PSR staining.

　　Results The body index, blood glucose, total cholesterol, triglyceride, 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); the action point time course (APD20, APD50, APD90) of the MD1-ko-high-fat group was significantly higher than that of the WT high-fat group (P<0.05); MD1-ko-high-fat group APD alternated Threshold value was significantly higher than that of WT high-fat group (P<0.05); the proportion of arrhythmia in MD1-ko-high-fat group was significantly higher than that of WT high-fat group (P<0.05); TLR4 in MD1-ko-high-fat group , MyD88 and P-CAMKII protein expressions were significantly higher than those in the WT high-fat group (all P<0. 05); the HW/BW ratio in the MD1-ko- high-fat group (7. 59±0. 78) was significantly higher than that in the WT high-fat group (7. 59±0. 78). lipid group ( 6. 07 ± 0. 58) (P < 0. 05). The cross-sectional area of cardiomyocytes in the MD1-ko-high-fat group (381. 23±35. 76) μm2 was significantly higher than that in the WT high-fat group (190. 15±25. 23) μm2 (P<0. 05); MD1 CollagenI, CollagenIII and TGF-β1 proteins in -ko-high-fat group were significantly higher than those in WT high-fat group (P<0.05).

　　Conclusion MD1 deficiency increases the susceptibility of high-fat diet-induced arrhythmias, mainly due to the enhanced activation of TLR4/MyD88 signaling pathway, which leads to left ventricular hypertrophy and fibrosis, and increases the expression of TLR4/MyD88 signaling pathway-related proteins.