健脾固胰饮对2型糖尿病大鼠炎症因子和肝组织TNF-α、IL-6 mRNA表达的影响
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摘要
目的：研究中药复方健脾固胰饮对2型糖尿病大鼠血清肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、C反应蛋白(CRP)及肝组织TNF-α、IL-6 mRNA表达的影响,探讨TNF-α、IL-6在糖尿病发病中的作用及中药复方治疗糖尿病的机制。
材料与方法：链脲佐菌素腹腔注射加高脂饲料喂养大鼠,造模2型糖尿病模型,设立对照组、模型组、中药1组、中药2组、罗格列酮组,健脾固胰饮灌胃治疗4周,检测空腹血糖、空腹胰岛素、血清胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白及TNF-α、IL-6、CRP,处死大鼠,取肝组织HE染色,并用逆转录RT-PCR方法测定肝组织TNF-α、IL-6 mRNA表达量。并通过与模型组对比,观察健脾固胰饮治疗糖尿病的疗效及作用机制。
结果：1)与对照组相比,模型组、中药1组、中药2组、罗格列酮组空腹血糖明显升高(P<0.01),与模型组相比,中药1组、中药2组、罗格列酮组空腹血糖明显下降(P<0.01)。中药1组、中药2组、罗格列酮组空腹血糖两两比较无显著性差异。2)与对照组相比,模型组、中药1组、中药2组、罗格列酮组空腹胰岛素明显升高(P<0.01),模型组、中药1组、中药2组、罗格列酮组空腹血胰岛素两两比较无显著性差异(P>0.05)。3)与对照组相比,模型组、中药1组、中药2组、罗格列酮组空腹血清胆固醇明显升高(P<0.01),罗格列酮组空腹血清胆固醇低于模型组、中药1组(P<0.01),与中药2组比较无显著性差异。4)空腹血甘油三酯比较,对照组、中药1组、中药2组、罗格列酮组明显低于模型组(P<0.01),中药1组空腹血甘油三酯高于中药2组(P<0.01),中药1组、中药2组与罗格列酮组比较无显著性差异(P>0.05)。5)高密度脂蛋白比较,模型组、中药1组、中药2组、罗格列酮组明显低于对照组(P<0.01),罗格列酮组与中药1组比较高密度脂蛋白无显著性差异,中药2组血清HDL高于中药1组(P<0.01)及罗格列酮组(P<0.05)。6)与对照组相比,空腹血低密度脂蛋白(LDL-C)模型组、中药1组、中药2组、罗格列酮组空腹明显升高(P<0.01),中药1组、中药2组略高于罗格列酮组(P<0.05),中药1组与中药2组比较无差异(P>0.05)。7)与对照组比较,模型组、中药1组、中药2组、罗格列酮组血清TNF-α明显升高(P<0.01),中药2组血清TNF-α低于中药1组、模型组(P<0.01),中药2组血清TNF-α与罗格列酮组无显著性差异(P>0.05)。8)血清儿-6,模型组、中药1组、中药2组、罗格列酮组均高于对照组(P<0.01),中药1组、中药2组、罗格列酮组3组间比较无显著性差异(P>0.05)。9)血清CRP中药2组与对照组比较无显著性差异(P>0.05),模型组、中药1组、罗格列酮组均高于对照组(P<0.01),中药2组低于中药1组(P>0.05),中药1组、中药2组与罗格列酮组比较均无显著性差异(P>0.05)。10)肝脏HE染色显示,中药2组大鼠肝细胞脂肪变性、肝小管周围炎性浸润较中药1组、罗格列酮组、模型组减轻,中药1组、罗格列酮组大鼠肝细胞脂肪变性与模型组比较无明显差异,对照组大鼠肝脏组织细胞基本正常。11)大鼠肝组织TNF-a mRNA表达量中药1组、中药2组、罗格列酮组均低于模型组(P<0.01),高于对照组(P<0.01),中药1组、中药2组与罗格列酮组间比较表达均无显著性差异(P>0.05)。12)与对照组比较,模型组、中药1组、中药2组、罗格列酮组糖尿病大鼠肝组织IL-6 mRNA表达增加(P<0.01),中药1组、中药2组、罗格列酮组较模型组表达降低(P<0.01),中药2组较中药1组、罗格列酮组降低更显著(P<0.05)。
结论：健脾固胰饮可降低2型糖尿病大鼠空腹血糖、改善血脂异常,该作用可能与其减少大鼠TNF-a、IL-6在肝组织的基因表达、降低血清TNF-a、IL-6、CRP从而减轻炎症反应有关。
Objective:To investigate the effect of Chinese medicine Jian Pi Gu Yi decoction on the concentration of TNF-α, IL-6 and CRP and the gene expression of TNF-αand IL-6 in liver of rats with diabetes mellitus 2, and discuss the role of TNF-a and IL-6 in the cause of the disease and the therapeutic action of the traditional chinese medicine.
Method:Rats model of Type 2 diabetes mellitus(T2DM) were induced with intraperitoneal injection of STZ and high fatty feeding. Wistar rats were divided into five groups:normal control, T2DM model group, Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group. The rats in experimental groups were fed with standard dose of Jian Pi Gu Yi decoction, high dose of Jian Pi Gu Yi decoction and Rosiglitazone respectively. Fasting blood glucose and insulin, cholesterol. triglyceride, TNF-α, IL-6 and CRP were tested in all the rats after 4 weeks of treatment. The mRNA expression of TNF-αand IL-6 were tested with RT-PCR and the histio-strcture of liver were observed.
Results:(1) Compared with normal control group, fasting blood glucose in other groups was higher (p<0.01). And compared with T2DM model group, fasting blood glucose was decreased significantly in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p<0.01). However, there was no significant difference in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(P>0.05). (2) Compared with normal control group, fasting blood insulin in other groups was higher (p<0.01). However, there was no significant difference in T2DM model group, Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(P>0.05). (3) Compared with normal control group, serum
cholesterol in other groups was higher (p<0.01). And serum cholesterol in Rosiglitazone group was decreased significantly compared with T2DM model group and Jian Pi Gu Yi decoction 1 group (p<0.01). However, there was no significant difference between Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(P>0.05).(4) Compared with T2DM model group, serum triglyceride in other groups was lower (p<0.01). And compared with Jian Pi Gu Yi decoction 2 group, serum triglyceride Jian Pi Gu Yi decoction 1 group was increased significantly(p<0.01). However, there was no significant difference in Jian Pi Gu Yi decoction 1 group. Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(P>0.05). (5) Compared with normal control group, serum HDL in other groups was lower (p<0.01). There was no significant difference between Jian Pi Gu Yi decoction 1 group and Rosiglitazone group. And the level of serum HDL in Jian Pi Gu Yi decoction 2 group was higher than Jian Pi Gu Yi decoction 1 group(p<0.01) and Rosiglitazone group(p<0.05). (6) Compared with normal control group, serum LDL-C in other groups was higher (p<0.01). And the level of LDL-C in Rosiglitazone group was lower than Jian Pi Gu Yi decoction 1 group and Jian Pi Gu Yi decoction 2 group (P<0.05). However, there was no significant difference between Jian Pi Gu Yi decoction 1 group and Jian Pi Gu Yi decoction 2 group. (7) Compared with normal control group, serum TNF-a in other groups was higher (p<0.01). And the level of serum TNF-αin Jian Pi Gu Yi decoction 2 group was lower than Jian Pi Gu Yi decoction 1 group and T2DM model group(p<0.01). However, there was no significant difference between Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p<0.05).(8) Compared with normal control group, serum IL-6 in other groups was higher (p<0.01). However, there was no significant difference in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p<0.05). (9) Compared with normal control group, serum CRP in T2DM model group, Jian Pi Gu Yi decoction 1 group and Rosiglitazone group were higher (p<0.01), and there was no significant difference between normal control group and Jian Pi Gu Yi decoction 2 group(p>0.05).And the level of CRP in Jian Pi Gu Yi decoction 2 group was lower than Jian Pi Gu Yi decoction 1 group (p<0.05). There was no significant difference in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p >0.05).(10) When observing the HE staining of liver, the histio-strcture in normal control group was normal. And the steatosis and hepatic inflammatory infiltration around the small tube in Jian Pi Gu Yi decoction 2 group were reduced compared with Jian Pi Gu Yi decoction 1 group, Rosiglitazone group and T2DM model group. Compared with T2DM model group. the steatosis and hepatic inflammatory infiltration around the small tube were reduced in Jian Pi Gu Yi decoction 1 and Rosiglitazone group. (11) Compared with T2DM model group, the mRNA expression of TNF-αin Jian Pi Gu Yi decoction 1 group. Jian Pi Gu Yi decoction 2 group and Rosiglitazone group were decreased(p<0.01) but was higher than normal control group(p<0.01). There was no significant difference in Jian Pi Gu Yi decoction 1 group. Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p >0.05). (12) Compared with normal control group, the mRNA expression of IL-6 in other groups was higher (p<0.01). and compared with T2DM model group, the mRNA expression of IL-6 in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group were decreased(p<0.01). The mRNA expression of IL-6 in Jian Pi Gu Yi decoction 2 group was significantly decreased than Jian Pi Gu Yi decoction 1 and Rosiglitazone group(p<0.05).
Conclusions:Jian Pi Gu Yi decoction can decrease Fasting blood glucose and cholesterol in diabetes mellitus 2 rats, Jian Pi Gu Yi decoction can decrease serum TNF-a and IL-6,too.and the effects may be the results of its decreasing action on the expression of TNF-αand IL-6 in rat liver.
材料与方法：链脲佐菌素腹腔注射加高脂饲料喂养大鼠,造模2型糖尿病模型,设立对照组、模型组、中药1组、中药2组、罗格列酮组,健脾固胰饮灌胃治疗4周,检测空腹血糖、空腹胰岛素、血清胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白及TNF-α、IL-6、CRP,处死大鼠,取肝组织HE染色,并用逆转录RT-PCR方法测定肝组织TNF-α、IL-6 mRNA表达量。并通过与模型组对比,观察健脾固胰饮治疗糖尿病的疗效及作用机制。
结果：1)与对照组相比,模型组、中药1组、中药2组、罗格列酮组空腹血糖明显升高(P<0.01),与模型组相比,中药1组、中药2组、罗格列酮组空腹血糖明显下降(P<0.01)。中药1组、中药2组、罗格列酮组空腹血糖两两比较无显著性差异。2)与对照组相比,模型组、中药1组、中药2组、罗格列酮组空腹胰岛素明显升高(P<0.01),模型组、中药1组、中药2组、罗格列酮组空腹血胰岛素两两比较无显著性差异(P>0.05)。3)与对照组相比,模型组、中药1组、中药2组、罗格列酮组空腹血清胆固醇明显升高(P<0.01),罗格列酮组空腹血清胆固醇低于模型组、中药1组(P<0.01),与中药2组比较无显著性差异。4)空腹血甘油三酯比较,对照组、中药1组、中药2组、罗格列酮组明显低于模型组(P<0.01),中药1组空腹血甘油三酯高于中药2组(P<0.01),中药1组、中药2组与罗格列酮组比较无显著性差异(P>0.05)。5)高密度脂蛋白比较,模型组、中药1组、中药2组、罗格列酮组明显低于对照组(P<0.01),罗格列酮组与中药1组比较高密度脂蛋白无显著性差异,中药2组血清HDL高于中药1组(P<0.01)及罗格列酮组(P<0.05)。6)与对照组相比,空腹血低密度脂蛋白(LDL-C)模型组、中药1组、中药2组、罗格列酮组空腹明显升高(P<0.01),中药1组、中药2组略高于罗格列酮组(P<0.05),中药1组与中药2组比较无差异(P>0.05)。7)与对照组比较,模型组、中药1组、中药2组、罗格列酮组血清TNF-α明显升高(P<0.01),中药2组血清TNF-α低于中药1组、模型组(P<0.01),中药2组血清TNF-α与罗格列酮组无显著性差异(P>0.05)。8)血清儿-6,模型组、中药1组、中药2组、罗格列酮组均高于对照组(P<0.01),中药1组、中药2组、罗格列酮组3组间比较无显著性差异(P>0.05)。9)血清CRP中药2组与对照组比较无显著性差异(P>0.05),模型组、中药1组、罗格列酮组均高于对照组(P<0.01),中药2组低于中药1组(P>0.05),中药1组、中药2组与罗格列酮组比较均无显著性差异(P>0.05)。10)肝脏HE染色显示,中药2组大鼠肝细胞脂肪变性、肝小管周围炎性浸润较中药1组、罗格列酮组、模型组减轻,中药1组、罗格列酮组大鼠肝细胞脂肪变性与模型组比较无明显差异,对照组大鼠肝脏组织细胞基本正常。11)大鼠肝组织TNF-a mRNA表达量中药1组、中药2组、罗格列酮组均低于模型组(P<0.01),高于对照组(P<0.01),中药1组、中药2组与罗格列酮组间比较表达均无显著性差异(P>0.05)。12)与对照组比较,模型组、中药1组、中药2组、罗格列酮组糖尿病大鼠肝组织IL-6 mRNA表达增加(P<0.01),中药1组、中药2组、罗格列酮组较模型组表达降低(P<0.01),中药2组较中药1组、罗格列酮组降低更显著(P<0.05)。
结论：健脾固胰饮可降低2型糖尿病大鼠空腹血糖、改善血脂异常,该作用可能与其减少大鼠TNF-a、IL-6在肝组织的基因表达、降低血清TNF-a、IL-6、CRP从而减轻炎症反应有关。
Objective:To investigate the effect of Chinese medicine Jian Pi Gu Yi decoction on the concentration of TNF-α, IL-6 and CRP and the gene expression of TNF-αand IL-6 in liver of rats with diabetes mellitus 2, and discuss the role of TNF-a and IL-6 in the cause of the disease and the therapeutic action of the traditional chinese medicine.
Method:Rats model of Type 2 diabetes mellitus(T2DM) were induced with intraperitoneal injection of STZ and high fatty feeding. Wistar rats were divided into five groups:normal control, T2DM model group, Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group. The rats in experimental groups were fed with standard dose of Jian Pi Gu Yi decoction, high dose of Jian Pi Gu Yi decoction and Rosiglitazone respectively. Fasting blood glucose and insulin, cholesterol. triglyceride, TNF-α, IL-6 and CRP were tested in all the rats after 4 weeks of treatment. The mRNA expression of TNF-αand IL-6 were tested with RT-PCR and the histio-strcture of liver were observed.
Results:(1) Compared with normal control group, fasting blood glucose in other groups was higher (p<0.01). And compared with T2DM model group, fasting blood glucose was decreased significantly in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p<0.01). However, there was no significant difference in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(P>0.05). (2) Compared with normal control group, fasting blood insulin in other groups was higher (p<0.01). However, there was no significant difference in T2DM model group, Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(P>0.05). (3) Compared with normal control group, serum
cholesterol in other groups was higher (p<0.01). And serum cholesterol in Rosiglitazone group was decreased significantly compared with T2DM model group and Jian Pi Gu Yi decoction 1 group (p<0.01). However, there was no significant difference between Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(P>0.05).(4) Compared with T2DM model group, serum triglyceride in other groups was lower (p<0.01). And compared with Jian Pi Gu Yi decoction 2 group, serum triglyceride Jian Pi Gu Yi decoction 1 group was increased significantly(p<0.01). However, there was no significant difference in Jian Pi Gu Yi decoction 1 group. Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(P>0.05). (5) Compared with normal control group, serum HDL in other groups was lower (p<0.01). There was no significant difference between Jian Pi Gu Yi decoction 1 group and Rosiglitazone group. And the level of serum HDL in Jian Pi Gu Yi decoction 2 group was higher than Jian Pi Gu Yi decoction 1 group(p<0.01) and Rosiglitazone group(p<0.05). (6) Compared with normal control group, serum LDL-C in other groups was higher (p<0.01). And the level of LDL-C in Rosiglitazone group was lower than Jian Pi Gu Yi decoction 1 group and Jian Pi Gu Yi decoction 2 group (P<0.05). However, there was no significant difference between Jian Pi Gu Yi decoction 1 group and Jian Pi Gu Yi decoction 2 group. (7) Compared with normal control group, serum TNF-a in other groups was higher (p<0.01). And the level of serum TNF-αin Jian Pi Gu Yi decoction 2 group was lower than Jian Pi Gu Yi decoction 1 group and T2DM model group(p<0.01). However, there was no significant difference between Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p<0.05).(8) Compared with normal control group, serum IL-6 in other groups was higher (p<0.01). However, there was no significant difference in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p<0.05). (9) Compared with normal control group, serum CRP in T2DM model group, Jian Pi Gu Yi decoction 1 group and Rosiglitazone group were higher (p<0.01), and there was no significant difference between normal control group and Jian Pi Gu Yi decoction 2 group(p>0.05).And the level of CRP in Jian Pi Gu Yi decoction 2 group was lower than Jian Pi Gu Yi decoction 1 group (p<0.05). There was no significant difference in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p >0.05).(10) When observing the HE staining of liver, the histio-strcture in normal control group was normal. And the steatosis and hepatic inflammatory infiltration around the small tube in Jian Pi Gu Yi decoction 2 group were reduced compared with Jian Pi Gu Yi decoction 1 group, Rosiglitazone group and T2DM model group. Compared with T2DM model group. the steatosis and hepatic inflammatory infiltration around the small tube were reduced in Jian Pi Gu Yi decoction 1 and Rosiglitazone group. (11) Compared with T2DM model group, the mRNA expression of TNF-αin Jian Pi Gu Yi decoction 1 group. Jian Pi Gu Yi decoction 2 group and Rosiglitazone group were decreased(p<0.01) but was higher than normal control group(p<0.01). There was no significant difference in Jian Pi Gu Yi decoction 1 group. Jian Pi Gu Yi decoction 2 group and Rosiglitazone group(p >0.05). (12) Compared with normal control group, the mRNA expression of IL-6 in other groups was higher (p<0.01). and compared with T2DM model group, the mRNA expression of IL-6 in Jian Pi Gu Yi decoction 1 group, Jian Pi Gu Yi decoction 2 group and Rosiglitazone group were decreased(p<0.01). The mRNA expression of IL-6 in Jian Pi Gu Yi decoction 2 group was significantly decreased than Jian Pi Gu Yi decoction 1 and Rosiglitazone group(p<0.05).
Conclusions:Jian Pi Gu Yi decoction can decrease Fasting blood glucose and cholesterol in diabetes mellitus 2 rats, Jian Pi Gu Yi decoction can decrease serum TNF-a and IL-6,too.and the effects may be the results of its decreasing action on the expression of TNF-αand IL-6 in rat liver.
引文
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[24]龙敏.C-反应蛋白和糖尿病[J].国外医学内分泌学分册,2002,22(2)：75-77.
[25]周秀艳,侯振江,刑桂芝.血清C反应蛋白与Ⅱ型糖尿病的关系[J].中国老年学杂志,2007,27(28)：145-146.
[26]Pickup JC. Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes[J]. Diabetes Care.2004,27(3):813-823.
[27]Slatnick MA, Beavers LS, Conner U, et al. Decrease expression of apMl in omental and subeultaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res,2000,1:81-88.
[28]Micheau O, Tschopp J.Induction of TNF receptorI-mediated apoptosis via two sequential signaling complexes [J].Cell,2003,114:181-190.
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[30]赵伟.糖尿病浊毒内蕴刍议[J].中医药信息,2009,26(5)：9-10.
[31]王文锐,陈晓雯.2型糖尿病下肢血管病变气阴两虚兼血瘀证证候学观察[J].中华中医药学刊,2010,28(3)：554-556.
[32]许筱颖,郭霞珍.浊毒致病理论初探[J].辽宁中医杂志,2007,34(1)：28.