氯沙坦和手把区域多肽对左旋谷氨酸钠大鼠血清胰岛素与胰高血糖素样肽-1的影响

Effects of losartan and handle region peptide on serum insulin and GLP-1 in rats neonatally treated with monosodium L-glutamate

目的通过氯沙坦、手把区域多肽(HRP)干预左旋谷氨酸钠(MSG)诱导的肥胖大鼠,比较大鼠不同状态下激素调控对血糖的影响。方法新生SD雄性大鼠出生后第2、4、6、8、10天皮下注射MSG,正常对照组(CON组)注射生理盐水。3周断奶后,MSG干预的大鼠随机分为MSG组、MSG+HRP组、MSG氯沙坦组(MSG+L组)、MSG+HRP+L组,予高脂饲料喂养,CON组则予基础饲料喂养。8周龄MSG+HRP组和MSG+HRP+L组以微泵泵入HRP,MSG+L组和MSG+HRP+L组予氯沙坦溶于大鼠饮水中。12周测大鼠体重、体长、脂肪湿重了解大鼠肥胖情况,通过OGTT评估大鼠血糖水平;ELISA法检测血清Insulin、Glucagon、GLP-1及Ghrelin空腹及糖负荷后30、60、120 min的水平。结果 (1)与CON组比较,MSG大鼠Lee’s指数、脂肪湿重明显增加,体长明显变小(P<0.05)。MSG+L及MSG+HRP+L组与MSG组比较,体重显著下降(P<0.05)。(2)MSG+HRP组OGTT血糖曲线下面积(AUC)大于CON和MSG组;MSG+L组小于MSG+HRP及MSG+HRP+L组(P<0.05)。(3)与CON组比较,其余四组Insulin、Glucagon、GLP-1水平在空腹状态、糖负荷后30 min、60 min均显著下降(P<0.05)。AUC结果显示,其余四组Insulin、Glucagon、GLP-1的AUC均小于CON组(P<0.05);MSG+HRP组Insulin、GLP-1的AUC均小于MSG组(P<0.05),而MSG+L组Insulin、GLP-1的AUC大于MSG组(P<0.05);且AUCInsulin与AUCGLP-1呈正相关(r=0.924,P<0.01);而MSG干预大鼠的四组之间AUCGlucagon无差异。(4)AUCGhrelin结果显示,MSG+HRP+L组AUC大于CON组(P<0.05)。AUCInsulin与AUCGhrelin无相关性。结论氯沙坦通过促进雄性MSG大鼠GLP-1分泌增加胰岛素水平而改善血糖状态,HRP则减少GLP-1分泌而减少胰岛素水平。

Objective To investigate the effects of hormones on plasma glucose after administration of losartan and handle region peptide （HRP） of monosodium L-glutamate （MSG） rats. Methods Newborn male rats were subcutaneously injected with MSG at the age of 2, 4, 6, 8, 10 days, while the control rats were injected with Nacl （CON group）. At the age of 3 weeks, the rats neonatally injected with MSG were randomly divided into MSG group, MSG＋HRP group, MSG＋L group, MSG＋HRP＋L group and fed with high-fat diet, while the control rats were fed with normal diet. From 8 to 12 weeks, MSG＋HRP and MSG＋HRP＋L group received HRP treatment, while MSG＋L and MSG＋HRP＋L received losartan treatment in drinking water. At the age of 12 weeks, oral glucose tolerance test （OGTT） was performed for evaluation of the glucose status. Obesity was evaluated by measuring weight, length, peritoneal fat of rats. The serum insulin, ghrelin and GLP-1 was detected by ELISA at 0 min, 30 min, 60 min, 120 min after glucose load. Results （1）Compared with the CON group, MSG rats had higher body weight, Lee＇s index and wet weight of peritoneal adipose tissue and lower body length（P〈0.05）. MSG＋L group and MSG＋HRP＋L group had lower body weight（P〈0.05）. （2）The AUCglucose after glucose load was higher in the MSG group compared with the CON group, whereas the MSG＋HRP had higher AUCglucose than the MSG group. The MSG＋L group had lower AUCglucose compared with the MSG＋HRP and MSG＋HRP＋L group（P〈0.05）. （3）Compare with CON group, the serum insulin and glucagon and GLP-1 of the else four groups was obviously decreased at 0, 30, 60 min and the AUC of insulin and glucagon and GLP-1 of the four groups were lower as well（P〈0.05）. The AUCGLP-1 and AUCInsulin of MSG＋HRP group was less than MSG group, but the AUCGLP-1 and AUCInsulin of MSG＋L group were higher than MSG group（P〈0.05）;The AUC of insulin was positive relevant with AUC of GLP-1（r=0.924,P〈0.01）;The result of AUCGlucagon did not have statistical different in the four groups which rats were subcutaneously injected with MSG. （4）The result of AUCGhrelin showed that MSG＋HRP＋L group were higher than CON group（P〈0.05）. The AUC of insulin was not related to AUC of Ghrelin. Conclusions Losartan can improve the glucose status by increasing the insulin releasing after glucose load, which caused by the elevation of GLP-1 secretion, whereas HRP decreases the serum insulin by lowering the GLP-1 secretion.