肥胖伴慢性束缚应激小鼠血压升高与孤束核去甲肾上腺素能神经元损伤的关系研究

Obesity Combined with Chronic Restraint Stress-Induced Hypertension in Mice Is Associated with the Damage of Noradrenergic Neurons in Nucleus Tractus Solitarii

目的探讨肥胖伴慢性束缚应激(chronic restraint stress,CRS)是否致小鼠血压升高及其与孤束核中间部(iNTS)损伤的关系。方法制作CRS小鼠模型,将51只小鼠分为低脂非束缚组(LF组)、低脂束缚组(LS组)、高脂非束缚组(HF组)、高脂束缚组(HS组);7 d束缚+3 d自由活动为一个周期,共4个周期(40 d);每个周期中第9天时检测小鼠体质量、并测量动脉收缩压,实验第40天时处死各组小鼠后取脑组织行免疫组织化学染色及免疫印迹检测胶质纤维状酸性蛋白(glial fibrillary acidic protein,GFAP)、酪氨酸羟化酶(tyrosine hydroxylase,TH)表达,取附睾脂肪垫免疫印迹检测血管内皮生长因子A(vascular endothelial growth factor,VEGFA)蛋白表达(代表脂肪组织血管密度)。结果在第40天时,HS组小鼠动脉收缩压明显高于其他三组小鼠,高脂喂养组(HF组和HS组)体质量增长明显;各组小鼠VEGFA蛋白表达差异无统计学意义;束缚组(LS组和HS组)小鼠脑组织iNTS星形胶质细胞活化,HS组iNTS TH表达减少;HF组、LS组小鼠血压均无异常变化;HS组血压普遍升高,其中37.5%小鼠出现高血压(动脉收缩压≥140 mmHg,1 mmHg=0.133 kPa)。结论肥胖伴慢性束缚应激可致小鼠动脉血压升高,且其机制与孤束核去甲肾上腺素能神经元损伤有关。

Objective To investigate whether obesity combined with chronic restraint stress(CRS)can increase blood pressure in mice and its relationship with the damage of the intermediate part of the nucleus tractus solitarius(iNTS).Methods The CRS mouse model was constructed,and 51 mice were assigned to four groups,low-fat diet non-restraint group(LF group),low-fat diet restraint group(LS group),high-fat diet non-restraint group(HF group),and high-fat diet restraint group(HS group).Interventions were carried out in four cycles(over the course of 40 consecutive days),with each cycle consisting of 7 days of restraint and 3 days of free movement.The body weight and the arterial systolic blood pressure of the mice were measured on the day 9 of every cycle.The mice were sacrificed on day 40 and the brain tissues of the mice were collected afterwards in order to perform immunohistochemical staining and Western blot to examine the expression of glial fibrillary acidic protein(GFAP)and tyrosine hydroxylase(TH).The protein expression of vascular endothelial growth factor A(VEGFA)was examined with Western blot on epididymal fat pad to assess the vascular density of lipid tissue.Results On day 40,the arterial systolic pressure of mice in HS group was significantly higher than that of mice in the three other groups.Body mass of high-fat diet group(HF group and HS group)increased significantly.Mice in the four groups did not present significant difference in VEGFA protein expression.INTS astrocytes were activated in the brain of mice in the restraint groups(LS group and HS group),and iNTS TH expression was decreased in HS group.Mice in HF group and LS group did not show abnormal changes in their blood pressure.Blood pressure of mice in the HS group generally rose,and hypertension(arterial systolic blood pressure≥140 mmHg,1 mmHg=0.133 kPa)was observed in 37.5%of the mice in this group.Conclusion Obesity combined with CRS may cause an increase in arterial blood pressure in mice,the mechanism of which may be related to the damage of noradrenergic neurons in the nucleus tractus solitarius.