庆大霉素通过调节大鼠慢性炎症控制高脂饮食对高血压的影响

Gentamicin reduces hypertension in high-fat diet-fed rats by modulation of chronic inflammation

目的探讨高脂喂食对大鼠内毒素、炎症因子和血压水平的影响及硫酸庆大霉素对其干预结果的观察。方法给予8周龄雄性SD大鼠适应性喂养1周后,分为对照组(普通饲料喂养)11只,高脂组(高脂饲料喂养)13只和庆大霉素组(高脂饲料喂养)13只,测得三组大鼠血压值作为基线水平,饲养4周,第5周开始每周监测大鼠血压,第9周开始,庆大霉素组给予硫酸庆大霉素灌胃干预,对照组和高脂组给予等量生理盐水灌胃。第13周结束,处死各组大鼠,检测大鼠血浆内毒素、IL-1β(白介素1β)浓度,检测大鼠血浆葡萄糖浓度、胰岛素浓度,用稳态模型评估胰岛素抵抗指数。结果实验初始收缩压对照组为(96.09±3.51)mmHg;高脂组为(93.28±4.12)mmHg;庆大霉素组为(92.30±6.26)mmHg,三组大鼠收缩压基线水平一致(P>0.05)。实验结束时高脂组大鼠收缩压(140.89±11.42)mmHg显著高于对照组(99.62±11.27)mmHg和庆大霉素组(94.64±9.59)mmHg,差异均有统计学意义(P<0.05),而对照组和庆大霉素组收缩压水平一致(P>0.05)。从实验初始至结束各组大鼠体质量每周行横向比较(P<0.05)。实验结束时庆大霉素组中的血浆内毒素浓度(0.10±0.02)EU/mL显著低于高脂组(0.14±0.02)EU/mL、显著高于对照组(0.07±0.01)EU/mL(P<0.05)。庆大霉素组中的IL-1β浓度(106.6±34.84)ng/mL显著低于高脂组(265.63±71.53)ng/mL(P<0.05),与对照组(90.90±26.67)ng/mL相比(P>0.05)。高脂组(1.24±0.19)mmol/L和庆大霉素组(1.27±0.30)mmol/l血浆总胆固醇水平均高于对照组(0.88±0.09)mmol/L(P<0.05),而高脂组和庆大霉素组胆固醇水平一致(P>0.05),庆大霉素组(0.43±0.13)mmol/L血浆低密度脂蛋白显著高于对照组(0.30±0.07)mmol/L(P<0.05)。庆大霉素组中的胰岛素抵抗(1.77±0.33)显著低于对照组(3.50±0.73)和高脂组(3.44±1.61)(P<0.05),而对照组和高脂组胰岛素抵抗水平一致(P>0.05)。结论高脂(高甘油三酯)喂食可导致大鼠收缩压升高、血浆内毒素和IL-1β水平增加,硫酸庆大霉素灌胃干预可能通过缓解机体低度炎症改善血压异常。高脂饲料喂养法建立的动物模型适合应用于建立单纯性高胆固醇血症,并不能建立肥胖大鼠模型。

Objective To investigate the effects of high-fat diet on endotoxin,inflammatory factors and blood pressure in rats,and observe the intervention effect of gentamycin sulfate.Methods 8-week-old male SD rats were adaptively fed for 1 week,then all of the experimental rats were randomly divided into control group[（Provide normal-diet）,n=11]and high-fat diet group[（Provide high-fat diet）,n=13],and gentamicin group[（Provide high-fat diet）,n=13].The blood pressure levels of the 3 groups were measured as baseline levels.And then,the blood pressure levels of rats were measured once a week from the fifth week.From the ninth weeks,the control group given normal saline（n=11）,high fat group（n=13）given normal saline,gentamicin group（n=13）received gentamicin sulfate intragastrically.All of the experimental rats were killed at the end of the 13 th week.The levels of plasma glucose,endotoxin,IL-1β,and insulin were measured,as well as HOMA insulin resistance index（HOMA-IR）was calculated.Results At the first week,there was no statistical significance in the levels of systolic blood pressure among the control group（96.09±3.51 mmHg）and the high-fat diet group（93.28±4.12 mmHg）as well as the gentamicin group（92.30±6.26 mmHg）（P〉0.05）.At the end of the experiment,the levels of systolic blood pressure in the high fat group（140.89±11.42 mmHg）were higher than that in the control group（99.62±11.27 mmHg）and gentamicin group（94.64±9.59 mmHg）（P〈0.05）.There was no statistical significance in the levels of systolic blood pressure between the control group and the gentamicin group.From the initial to the end of the experiment in each group of rats body mass per week transversal comparison（P〈0.05）.At the end of the experiment,the concentration of plasma endotoxin in the gentamicin group（0.10±0.02 EU/ml）was significantly lower than that in the high-fat diet group（0.14±0.02 EU/ml）,but significantly higher than that in the control group（0.07±0.01 EU/ml）（P〈0.05）.The concentration of IL-1βin the gentamicin group（106.6±34.84 ng/ml）was significantly lower than those in the high-fat diet group（265.63±71.53 ng/ml）（P〈0.05）.The plasma total cholesterol of high fat group（1.24＋0.19 mmol/l）and gentamicin group（1.27＋0.30 mmol/l）were higher than the control group（0.88＋0.09 mmol/l）（P〈0.05）.There was no difference in the cholesterol level between the high-fat group and the gentamycin group（P〉0.05）.The plasma low density lipoprotein（0.43 ＋ 0.13 mmol/l）of gentamicin group was significantly higher than that of the control group（0.30＋0.07 mmol/l）（P〈0.05）.The insulin resistance in the gentamicin group（1.77±0.33）was lower than those in the control group（3.50±0.73）and the high fat group（3.44±1.61）（P〈0.05）.There was no statistical difference in insulin resistance between the control group and the highfat group（P〉0.05）.Conclusion High fat（high triglyceride）feeding results in elevated blood pressure level and increases levels of plasma endotoxin and IL-1βin rats.The intervention of gentamicin sulfate may improve blood pressure by lowing levels of inflammation in the body.The animal model established by high fat feed method is suitable for the establishment of simple hypercholesterolemia,and the model of obese rats cannot be established.