人工寒潮促发2型糖尿病大鼠卒中前状态脑组织ET-1与CGRP含量的变化
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摘要
目的通过观察2型糖尿病大鼠经历人工寒潮卒中发病前脑组织内皮素-1(ET-1)与降钙素基因相关肽(CGRP)含量的变化,初步探讨ET-1和CGRP对易卒中状态的影响,并借以预测中风的发生。
方法应用链脲左菌素加高糖高脂饮食复制2型糖尿病(DM)模型,将复制成功的DM模型组与对照组大鼠各分为寒潮组与非寒潮组。寒潮组置于人工气候箱中,温度设置以22℃12小时,4℃12小时为1天循环,共3天。非寒潮组置于温度22℃的人工气候箱共3天。在人工气候箱处理前后测量体重、血糖,以寒潮3天为研究终点,在研究终点将大鼠灌注后断头取脑(除死亡鼠)用于免疫组化,每只大鼠随机取5张切片作免疫组化检测大鼠脑组织的ET-1与CGRP蛋白的表达,发生卒中者被剔除卒中前状态分析。
结果
1.DM模型的复制:DM组在注射STZ后表现为多饮、多食、多尿及体重下降典型糖尿病症状;并且出现血糖高,胰岛素升高,胰岛素敏感性下降,有统计学意义。
2.脑组织内ET-1和CGRP的蛋白(免疫组化)表达:DM模型组脑组织内ET-1和CGRP的表达均高于对照组(P=0.000)。经过寒潮干预,DM寒潮组ET-1含量明显高于非寒潮组(P=0.003),CGRP表达却明显下降(P=0.000);对照组两者含量无明显改变。
结论
1.经高糖高脂饲料喂养4周后,再经腹腔注射小剂量链脲佐菌素,可以建立2型糖尿病大鼠动物模型。
2.2型糖尿病大鼠组织内ET-1、CGRP表达升高。2型糖尿病会导致血管内皮功能的改变。
3. DM寒潮组与DM非寒潮组比较,大鼠脑组织ET-1含量明显增高,CGRP表达显著降低;对照寒潮组与非寒潮组相比,大鼠脑组织ET-1与CGRP含量无明显改变。寒潮做为诱因会进一步加重2型糖尿病大鼠血管内皮功能的损害,导致血管舒缩功能的异常,增加脑卒中的发病风险;而对正常大鼠血管功能无明显影响。
Objective We have observed the rats modes of type 2 diabetes mellitus to study the contents changes of ET-1 and CGRP before the stroke under artificial cold exposure (ACE), to evaluate the influence of the endothelin-1(ET-1) and CGRP on Stroke-prone state and to predict the occurrence of stroke.
Methods We establish a rats modes of type 2 diabetes mellitus(DM) by feeding high sugar and fat diet and subsequently injecting small dose streptozotocin(STZ). DM model rats and normal control rats were randomly assigned two groups:ACE and non-ACE..The ACE group was designed as 3 cycles of 12h light of 22℃and 12h dark of 4℃.The non-ACE group was kept at 22℃throughout the experiment. Body weight and blood glucose were measured before and after ACE treatment. Set the 3 days cold exposure as the end point, the rat brains were removed quickly and then perfusion (except dead mouse) for immunohistochemistry in the study endpoint. Before stroke occurred, every 5 sections were taken randomly from each rats used for immunohistochemical to detection the protein expression of ET-1 and calcitonin gene-related peptide(CGRP) in rat brain vascular endothelial. The stroke rats were out of the analysis.
Result
1.Replication of DM model: DM group showed the typical symptoms of diabetes of human such as more drinking, eating, polyuria and weight loss after injection of STZ; and emerged hyperglycemia, hyperinsulinmia and insulin resistance, which showed the statistical significance.
2.The protein expression of ET-1 and CGRP(immunohistochemistry) in the brain tissue: In DM model group, the expression of ET-1 and CGRP in the brain tissue were higher (P=0.000) than the control group. After ACE treatment, in DM group, ET-1 were significantly higher than non-ACE group(P=0.003), while CGRP was significantly lower than the non-ACE group (P=0.000); and there were showed no significant changes of ET-1 and CGRP in the control group.
Conclusion
1. We successfuly establish the rat model of type 2 diabetes mellitus by fed with high sugar and fat diet for 4 weeks,rats were injected a low dose of STZ intrapenitoneally.
2.The expression of ET-1 and CGRP could increase in type 2 diabetic rats.Type 2 diabetes could change the vascular endothelial function.
3. In DM group, ET-1 were significantly higher while CGRP was significantly lower; and there were showed no significant changes of ET-1 and CGRP in the control group.Cold as a incentives will further aggravate the damage of vascular endothelial function, which result the vasomotor function disorder then forming an environment conducive stroke which is closer to pre-stroke state.
方法应用链脲左菌素加高糖高脂饮食复制2型糖尿病(DM)模型,将复制成功的DM模型组与对照组大鼠各分为寒潮组与非寒潮组。寒潮组置于人工气候箱中,温度设置以22℃12小时,4℃12小时为1天循环,共3天。非寒潮组置于温度22℃的人工气候箱共3天。在人工气候箱处理前后测量体重、血糖,以寒潮3天为研究终点,在研究终点将大鼠灌注后断头取脑(除死亡鼠)用于免疫组化,每只大鼠随机取5张切片作免疫组化检测大鼠脑组织的ET-1与CGRP蛋白的表达,发生卒中者被剔除卒中前状态分析。
结果
1.DM模型的复制:DM组在注射STZ后表现为多饮、多食、多尿及体重下降典型糖尿病症状;并且出现血糖高,胰岛素升高,胰岛素敏感性下降,有统计学意义。
2.脑组织内ET-1和CGRP的蛋白(免疫组化)表达:DM模型组脑组织内ET-1和CGRP的表达均高于对照组(P=0.000)。经过寒潮干预,DM寒潮组ET-1含量明显高于非寒潮组(P=0.003),CGRP表达却明显下降(P=0.000);对照组两者含量无明显改变。
结论
1.经高糖高脂饲料喂养4周后,再经腹腔注射小剂量链脲佐菌素,可以建立2型糖尿病大鼠动物模型。
2.2型糖尿病大鼠组织内ET-1、CGRP表达升高。2型糖尿病会导致血管内皮功能的改变。
3. DM寒潮组与DM非寒潮组比较,大鼠脑组织ET-1含量明显增高,CGRP表达显著降低;对照寒潮组与非寒潮组相比,大鼠脑组织ET-1与CGRP含量无明显改变。寒潮做为诱因会进一步加重2型糖尿病大鼠血管内皮功能的损害,导致血管舒缩功能的异常,增加脑卒中的发病风险;而对正常大鼠血管功能无明显影响。
Objective We have observed the rats modes of type 2 diabetes mellitus to study the contents changes of ET-1 and CGRP before the stroke under artificial cold exposure (ACE), to evaluate the influence of the endothelin-1(ET-1) and CGRP on Stroke-prone state and to predict the occurrence of stroke.
Methods We establish a rats modes of type 2 diabetes mellitus(DM) by feeding high sugar and fat diet and subsequently injecting small dose streptozotocin(STZ). DM model rats and normal control rats were randomly assigned two groups:ACE and non-ACE..The ACE group was designed as 3 cycles of 12h light of 22℃and 12h dark of 4℃.The non-ACE group was kept at 22℃throughout the experiment. Body weight and blood glucose were measured before and after ACE treatment. Set the 3 days cold exposure as the end point, the rat brains were removed quickly and then perfusion (except dead mouse) for immunohistochemistry in the study endpoint. Before stroke occurred, every 5 sections were taken randomly from each rats used for immunohistochemical to detection the protein expression of ET-1 and calcitonin gene-related peptide(CGRP) in rat brain vascular endothelial. The stroke rats were out of the analysis.
Result
1.Replication of DM model: DM group showed the typical symptoms of diabetes of human such as more drinking, eating, polyuria and weight loss after injection of STZ; and emerged hyperglycemia, hyperinsulinmia and insulin resistance, which showed the statistical significance.
2.The protein expression of ET-1 and CGRP(immunohistochemistry) in the brain tissue: In DM model group, the expression of ET-1 and CGRP in the brain tissue were higher (P=0.000) than the control group. After ACE treatment, in DM group, ET-1 were significantly higher than non-ACE group(P=0.003), while CGRP was significantly lower than the non-ACE group (P=0.000); and there were showed no significant changes of ET-1 and CGRP in the control group.
Conclusion
1. We successfuly establish the rat model of type 2 diabetes mellitus by fed with high sugar and fat diet for 4 weeks,rats were injected a low dose of STZ intrapenitoneally.
2.The expression of ET-1 and CGRP could increase in type 2 diabetic rats.Type 2 diabetes could change the vascular endothelial function.
3. In DM group, ET-1 were significantly higher while CGRP was significantly lower; and there were showed no significant changes of ET-1 and CGRP in the control group.Cold as a incentives will further aggravate the damage of vascular endothelial function, which result the vasomotor function disorder then forming an environment conducive stroke which is closer to pre-stroke state.
引文
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[2] Feigin VL, Nikitin YP, Bots ML, et al. A population-based study of the associations of strke occurrence with weather parameters in Siberia[J]. Eur J Neurol,2000,7(2): 171-178.
[3] Hong YC, Rha JH, Lee JT, Ha EH, Kwon HJ, Kim H. Ischemic stroke associated with decrease in temperature[J]. Epidemiology,2003,14(4): 473-478.
[4]解龙昌,黄如训,李长新等.人工寒潮促发脑卒中的实验研究[J].中国神经精神疾病杂志,2004,30(3):198-201.
[5]黄如训.卒中前状态和启动因子[J].中国神经精神疾病杂志,2005,31(1):73-75.
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