降糖益肾方干预氧化应激反应改善MKR转基因2型糖尿病鼠肾损伤的实验研究
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摘要
目的通过研究高脂喂饲的MKR转基因2型糖尿病小鼠肾损伤模型(简称高脂MKR鼠),观察降糖益肾方对其肾脏功能和病理损伤及肾脏MDA含量、SOD和GSH-Px活性的影响,初步探讨降糖益肾方对高脂MKR鼠血糖、胰岛素水平、肾脏结构和功能及氧化应激损伤的影响。
方法
1.高脂MKR鼠肾损伤模型的实验研究：选取7周龄MKR鼠20只,雌雄各半,根据血糖和体重随机分为基础饲料喂饲的MKR鼠组和高脂喂饲的MKR鼠组,每组10只。另设野生C57BL/6鼠(C57鼠)10只同期对照。其中MKR高脂组以高脂饲料喂养,其它以基础饲料喂养,连续8周。于15周末观察其肾脏病理改变,测定其空腹血糖、糖耐量、血脂、血清胰岛素水平、BUN、Cr及UmA1b、尿β2-MG含量。
2.降糖益肾方对高脂喂饲的MKR鼠肾脏功能及氧化应激损伤影响的实验研究：将40只7周龄MKR鼠根据血糖和体重分层,随机分为MKR鼠组,高脂模型组,中药治疗组,西药阳性对照组。MKR鼠组用基础饲料喂养,其余各组均以高脂饲料喂养,连续喂养8周,将各组小鼠喂养至15周龄开始灌胃。中药治疗组给予降糖益肾方、西药阳性对照组给予糖适平加贝那普利,灌胃治疗30天。同时MKR鼠组和高脂模型组分别予蒸馏水灌胃30天。每日灌胃一次。30天后收集标本,检测空腹血糖、血清胰岛素、BUN、Cr、RBP-4和PAI含量,UmA1b和尿β2-MG含量、肾脏MDA含量、SOD和GSH-Px活性等。所有实验数据均用SPSS15.0软件进行统计学处理。
结果
1.高脂组MKR鼠于15周时出现明显肾脏病理形态学改变,空腹血糖、血脂、血清胰岛素水平、BUN、Cr及UmAlb、尿β2-MG含量均较野生C57BL/6鼠明显升高,糖耐量异常。与基础饲料喂饲组MKR鼠相比进一步升高,差异具有统计学意义(P<0.01或P<0.05)。
2.降糖益肾方组MKR鼠血糖、血胰岛素水平,血清BUN、Cr、RBP-4和PAI含量,UmAlb和尿β2-MG及肾脏皮质MDA含量均显著低于高脂模型组(P<0.01或P<0.05)；SOD和GSH-Px活性与高脂模型组比较明显增高,差异具有统计学意义(P<0.01)。
结论
1.MKR鼠与野生鼠对照实验表明,MKR转基因2型糖尿病鼠存在明显肾脏损伤,而高脂喂饲可以进一步加重其肾脏损伤。
2.降糖益肾方具有降低血糖、改善糖耐量、改善高胰岛素血症、调节蛋白代谢、改善肾功能及肾脏病理结构等的作用。
3.降糖益肾方改善2型糖尿病肾损伤的作用机制可能与干预氧化应激反应,改善肾脏功能及病理损伤有关。降糖益肾方可能通过抑制氧化应激反应,增强抗氧化酶活性,提高肾组织总抗氧化能力,减少脂质过氧化产物产生,降低氧化应激水平,从而减轻糖尿病时肾脏的氧化应激损伤,改善肾脏功能及病理损伤,调节蛋白代谢,从而起到减轻肾脏损伤和延缓糖尿病肾损伤发生、发展的作用。
Objective:
Studying on MKR transgenic Mice with kidney damage of type 2 diabetes (Be short for high-fat MKR mice)that fed with high fat diet, to observe the changes of JiangTang YiShen decoction on the structure and function of the renal pathology, the renal MDA content, SOD and GSH-Px activity. And preliminarily investigate the effects of JiangTang YiShen decoction on the levels of blood glucose, serum insulin, structure and function of the renal pathology, and the damages of oxidative stress in the kidney of MKR mice.
Methods:
1. The experimental model study on MKR mice of the type 2 diabetic kidney damage:Twenty 7-week-old MKR mice were randomly divided into two groups after stratifying by the FBG and body weight.i.e,10 mice fed by normal diet, and the others fed by high fat diet. At the same time,10 C57BL/6 wild mice were selected as the control group. The three groups were fed for eight weeks. At the end of 15th week, all mice were killed to investigate the renal pathological changes, and the contents of blood glucose, glucose tolerance, blood-fat, serum insulin, blood urea nitrogen (BUN), creatinine (Cr), urine MAlb andβ2-MG were determined, respectively.
2. The effects of JiangTang YiShen decoction on the renal functions and oxidative stress damages of MKR mice fed by high fat diet:Fourty 7-week-old MKR mice were randomly divided into four groups after stratifying by FBG and body weight.i.e, MKR group, model group, JiangTang YiShen decoction group(JYD), and control group. MKR group were fed by normal diet for eight weeks, and others were fed by high fat diet for eight weeks. At the 15th week, the JYD group was treated with JiangTang YiShen decoction, the control group was treated with Gliquidone Benazepril, and other two groups were treated with distilled water. All the groups were administered intragastrically once a day for thirty days. All mice were killed at the end of thirty days, and then, the content of blood glucose, serum insulin, blood urea nitrogen (BUN), creatinine (Cr), serum RBP-4 and PAI, urine UmAlb andβ2-MG, renal MDA, SOD and GSH-Px activity of each group were tested. All the data were analyzed with SPSS (America, SPSS Inc., v15.0).
Results:
1. The renal pathological morphology of MKR mice significantly changed on 15th week. The contents of blood glucose, glucose tolerance, blood-fat, serum insulin, blood urea nitrogen (BUN), creatinine (Cr), urine MAlb andβ2-MG in the mice fed by high fat diet were significantly higher than those in C57BL/6 wild mice and the MKR mice fed by normal diet (P <0.01).
2. The changes of renal pathology in the MKR mice treated with JiangTang YiShen decoction (JYD group) were significantly improved compared with the model group. The contents of fasting blood glucose, serum insulin, blood urea nitrogen (BUN), creatinine (Cr), serum RBP-4 and PAI, urine MAlb,β2-MG, renal MDA in JYD group were significantly lower than those in model group(P<0.01), while the activity of renal SOD and GSH-Px in JYD group mice were significantly higher than model group (P<0.01).
Conclusion:
1. The results of MKR and wild mice showed that there were renal damages in MKR mice, and the damages were worse in MKR mice fed by high fat diet.
2. JiangTang YiShen decoction might reduce the level of blood glucose and serum insulin, improve the glucose tolerance, make the renal function and kidney pathological structure better and adjust protein metabolism, etc.
3. The mechanism of JiangTang YiShen decoction to improve the kidney damage of type 2 diabetes may be about interfering with the activities of oxidative stress and improving the function and pathological structure of kidney. Through inhibiting the activities of oxidative stress, increasing the activity of antioxidase and the total antioxidant capacity of renal tissue, and reducing peroxidize substances and oxidative stress level, JiangTang YiShen decoction could abate oxidative damage of renal with diabetes, improve the structure and function of renal pathology, and adjust protein metabolism, all of which could relieve renal damage and reduce the occurrence and development of diabetes.
方法
1.高脂MKR鼠肾损伤模型的实验研究：选取7周龄MKR鼠20只,雌雄各半,根据血糖和体重随机分为基础饲料喂饲的MKR鼠组和高脂喂饲的MKR鼠组,每组10只。另设野生C57BL/6鼠(C57鼠)10只同期对照。其中MKR高脂组以高脂饲料喂养,其它以基础饲料喂养,连续8周。于15周末观察其肾脏病理改变,测定其空腹血糖、糖耐量、血脂、血清胰岛素水平、BUN、Cr及UmA1b、尿β2-MG含量。
2.降糖益肾方对高脂喂饲的MKR鼠肾脏功能及氧化应激损伤影响的实验研究：将40只7周龄MKR鼠根据血糖和体重分层,随机分为MKR鼠组,高脂模型组,中药治疗组,西药阳性对照组。MKR鼠组用基础饲料喂养,其余各组均以高脂饲料喂养,连续喂养8周,将各组小鼠喂养至15周龄开始灌胃。中药治疗组给予降糖益肾方、西药阳性对照组给予糖适平加贝那普利,灌胃治疗30天。同时MKR鼠组和高脂模型组分别予蒸馏水灌胃30天。每日灌胃一次。30天后收集标本,检测空腹血糖、血清胰岛素、BUN、Cr、RBP-4和PAI含量,UmA1b和尿β2-MG含量、肾脏MDA含量、SOD和GSH-Px活性等。所有实验数据均用SPSS15.0软件进行统计学处理。
结果
1.高脂组MKR鼠于15周时出现明显肾脏病理形态学改变,空腹血糖、血脂、血清胰岛素水平、BUN、Cr及UmAlb、尿β2-MG含量均较野生C57BL/6鼠明显升高,糖耐量异常。与基础饲料喂饲组MKR鼠相比进一步升高,差异具有统计学意义(P<0.01或P<0.05)。
2.降糖益肾方组MKR鼠血糖、血胰岛素水平,血清BUN、Cr、RBP-4和PAI含量,UmAlb和尿β2-MG及肾脏皮质MDA含量均显著低于高脂模型组(P<0.01或P<0.05)；SOD和GSH-Px活性与高脂模型组比较明显增高,差异具有统计学意义(P<0.01)。
结论
1.MKR鼠与野生鼠对照实验表明,MKR转基因2型糖尿病鼠存在明显肾脏损伤,而高脂喂饲可以进一步加重其肾脏损伤。
2.降糖益肾方具有降低血糖、改善糖耐量、改善高胰岛素血症、调节蛋白代谢、改善肾功能及肾脏病理结构等的作用。
3.降糖益肾方改善2型糖尿病肾损伤的作用机制可能与干预氧化应激反应,改善肾脏功能及病理损伤有关。降糖益肾方可能通过抑制氧化应激反应,增强抗氧化酶活性,提高肾组织总抗氧化能力,减少脂质过氧化产物产生,降低氧化应激水平,从而减轻糖尿病时肾脏的氧化应激损伤,改善肾脏功能及病理损伤,调节蛋白代谢,从而起到减轻肾脏损伤和延缓糖尿病肾损伤发生、发展的作用。
Objective:
Studying on MKR transgenic Mice with kidney damage of type 2 diabetes (Be short for high-fat MKR mice)that fed with high fat diet, to observe the changes of JiangTang YiShen decoction on the structure and function of the renal pathology, the renal MDA content, SOD and GSH-Px activity. And preliminarily investigate the effects of JiangTang YiShen decoction on the levels of blood glucose, serum insulin, structure and function of the renal pathology, and the damages of oxidative stress in the kidney of MKR mice.
Methods:
1. The experimental model study on MKR mice of the type 2 diabetic kidney damage:Twenty 7-week-old MKR mice were randomly divided into two groups after stratifying by the FBG and body weight.i.e,10 mice fed by normal diet, and the others fed by high fat diet. At the same time,10 C57BL/6 wild mice were selected as the control group. The three groups were fed for eight weeks. At the end of 15th week, all mice were killed to investigate the renal pathological changes, and the contents of blood glucose, glucose tolerance, blood-fat, serum insulin, blood urea nitrogen (BUN), creatinine (Cr), urine MAlb andβ2-MG were determined, respectively.
2. The effects of JiangTang YiShen decoction on the renal functions and oxidative stress damages of MKR mice fed by high fat diet:Fourty 7-week-old MKR mice were randomly divided into four groups after stratifying by FBG and body weight.i.e, MKR group, model group, JiangTang YiShen decoction group(JYD), and control group. MKR group were fed by normal diet for eight weeks, and others were fed by high fat diet for eight weeks. At the 15th week, the JYD group was treated with JiangTang YiShen decoction, the control group was treated with Gliquidone Benazepril, and other two groups were treated with distilled water. All the groups were administered intragastrically once a day for thirty days. All mice were killed at the end of thirty days, and then, the content of blood glucose, serum insulin, blood urea nitrogen (BUN), creatinine (Cr), serum RBP-4 and PAI, urine UmAlb andβ2-MG, renal MDA, SOD and GSH-Px activity of each group were tested. All the data were analyzed with SPSS (America, SPSS Inc., v15.0).
Results:
1. The renal pathological morphology of MKR mice significantly changed on 15th week. The contents of blood glucose, glucose tolerance, blood-fat, serum insulin, blood urea nitrogen (BUN), creatinine (Cr), urine MAlb andβ2-MG in the mice fed by high fat diet were significantly higher than those in C57BL/6 wild mice and the MKR mice fed by normal diet (P <0.01).
2. The changes of renal pathology in the MKR mice treated with JiangTang YiShen decoction (JYD group) were significantly improved compared with the model group. The contents of fasting blood glucose, serum insulin, blood urea nitrogen (BUN), creatinine (Cr), serum RBP-4 and PAI, urine MAlb,β2-MG, renal MDA in JYD group were significantly lower than those in model group(P<0.01), while the activity of renal SOD and GSH-Px in JYD group mice were significantly higher than model group (P<0.01).
Conclusion:
1. The results of MKR and wild mice showed that there were renal damages in MKR mice, and the damages were worse in MKR mice fed by high fat diet.
2. JiangTang YiShen decoction might reduce the level of blood glucose and serum insulin, improve the glucose tolerance, make the renal function and kidney pathological structure better and adjust protein metabolism, etc.
3. The mechanism of JiangTang YiShen decoction to improve the kidney damage of type 2 diabetes may be about interfering with the activities of oxidative stress and improving the function and pathological structure of kidney. Through inhibiting the activities of oxidative stress, increasing the activity of antioxidase and the total antioxidant capacity of renal tissue, and reducing peroxidize substances and oxidative stress level, JiangTang YiShen decoction could abate oxidative damage of renal with diabetes, improve the structure and function of renal pathology, and adjust protein metabolism, all of which could relieve renal damage and reduce the occurrence and development of diabetes.
引文
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