高脂饮食对小鼠呼吸道和背根神经节瞬时感受器电位阳离子通道香草酸-1的影响

Effect of high-fat diet on expression of transient receptor potential vanilloid 1 in respiratory tract and dorsal root ganglion of mice

目的探讨高脂饮食对瞬时感受器电位阳离子通道香草酸-1(TRPV1)在小鼠呼吸系统和背根神经节(DRG)上的表达变化,并研究其对感觉神经元兴奋性的影响。方法将C57BL/6小鼠20只随机分成普通饲料组和高脂饲料组,每组10只。分别喂养相应饲料并监测体重。喂养7周后取两组小鼠肺叶、支气管组织,以及胸3~4段DRG行免疫组化染色检测TRPV1表达水平,并用膜片钳测量DRG动作电位和TRPV1电流。结果经7周饲养后,高脂饲料组平均增重(6.4±2.6 g)显著大于普通饲料组(2.3±0.5 g)(P<0.001)。高脂饲料组支气管、肺泡和DRG上TRPV1的阳性表达均明显高于普通饲料组(P<0.05)。高脂饲料组DRG上TRPV1电流强度和动作电位激发数目较普通饲料组均明显升高(P<0.05)。结论高脂饮食引起小鼠体重明显增加,导致小鼠呼吸系统和外周感觉神经元中TRPV1呈现高表达和易激惹高兴奋性,提示TRPV1可能是导致支气管超高反应病理生理机制中的一个重要因子。

Objective To investigate the effect of high-fat diet on the expression of transient receptor potential vanilloid 1 （TRPV1） in the respiratory system and the dorsal root ganglion （DRG） of mice, as well as its effect on the excitability of sensory neurons. Methods A total of 20 C57BL/6 mice were randomly divided into normal-diet （ND） group and high-fat diet （HFD） group, with 10 mice in each group. The mice were given corresponding diets and body weights were monitored. After 7 weeks of feeding, lung tissue, bronchial tissue, and DRG at thoracic segments 3-4 were collected and immunohistochemical staining was performed. A patch clamp was used to measure the number of action potentials and TRPV1 current intensity in the DRG. Results After 7 weeks of feeding, the HFD group had significantly greater mean weight gain than the ND group （6.4±2.6 g vs 2.3±0.5 g; P〈0.001）. The HFD group had significantly higher expression of TRPV1 in the bronchus, pulmonary alveoli, and DRG than the ND group （P〈0.05）. Compared with the ND group, the HFD group had significant increases in the TRPVl current intensity and number of action potentials in the DRG （P〈0.05）. Conclusions High-fat diet induces a significant increase in body weight and leads to high expression of TRPV 1 and high excitability in the respiratory system and the peripheral sensory neurons. This suggests that TRPV 1 may be an important factor in the physiopathological mechanisms of bronchial hyperresponsiveness.