α1-抗胰蛋白酶对Ⅱ型糖尿病的药效学研究
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摘要
目的通过建模研究α1-抗胰蛋白酶(AAT)治疗糖尿病的动物药效学。方法将大鼠造成Ⅱ型糖尿病模型,选择血糖值在15~30 mmol/L者用于实验组,AAT分为高(11.5 mg/kg)、低(5.75 mg/kg)两个剂量组,盐酸二甲双胍缓释片做阳性对照。测定血清血糖(GLU)、肌酐(Cre)、尿素氮(BUN)、总蛋白(TP)、白蛋白(ALB)、球蛋白(GLB)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),并进行病理组织学检测。结果与模型组比较,二甲双胍组、AAT低剂量组、AAT高剂量组中GLU均明显降低,差异有统计学意义(P<0.05);TP在二甲双胍组、AAT低剂量组有升高趋势,在AAT高剂量组有降低趋势;三个受试药组TC明显降低;TG在二甲双胍组有升高趋势,在AAT低、高剂量组中均明显降低(P<0.05)。结论 AAT对Ⅱ型糖尿病大鼠模型有明显的降糖、降脂作用,AAT低剂量对TP有升高的趋势,可改善实验动物肾脏和胰腺内胰岛形态的作用。
Objective The pharmacodynamics of α1-antitrypsin(AAT)in the treatment of diabetes mellitus was studied by modeling.Methods Model rats with type 2 diabetes with blood glucose level of 15~30 mmol/L were selected as the experimental group.High dose group was treated with AAT 11.5 mg/kg and the low dose group was was treated with AAT5.75 mg/kg.The positive control group was treated with metformin hydrochloride sustained-release tablet.The serum levels of glucose(GLU),creatinine(Cre),urea nitrogen(BUN),total protein(TP),albumin(ALB),globulin(GLB),triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDLC)were assyed.Histopathological examination was also performed.Results Compared with the model group,the GLU was significantly lower in the metformin group,AAT low-dose group,and AAT high-dose group,differences are statistically significant(P<0.05).TP increased in the metformin group and AAT low-dose group,and decreased in the AAT high-dose group.TC decreased significantly in the three trial groups.TG increased in the metformin group,and significantly decreased in the AAT low-dose group and AAT high-dose group.Conclusion The results showed that AAT had obvious hypoglycemic and lipid-lowering effects on type 2 diabetic rats,and low dose of AAT had a tendency to increase the total protein,which could improve the kidney and pancreaticislet morphology in the experimental animals.
Objective The pharmacodynamics of α1-antitrypsin(AAT)in the treatment of diabetes mellitus was studied by modeling.Methods Model rats with type 2 diabetes with blood glucose level of 15~30 mmol/L were selected as the experimental group.High dose group was treated with AAT 11.5 mg/kg and the low dose group was was treated with AAT5.75 mg/kg.The positive control group was treated with metformin hydrochloride sustained-release tablet.The serum levels of glucose(GLU),creatinine(Cre),urea nitrogen(BUN),total protein(TP),albumin(ALB),globulin(GLB),triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDLC)were assyed.Histopathological examination was also performed.Results Compared with the model group,the GLU was significantly lower in the metformin group,AAT low-dose group,and AAT high-dose group,differences are statistically significant(P<0.05).TP increased in the metformin group and AAT low-dose group,and decreased in the AAT high-dose group.TC decreased significantly in the three trial groups.TG increased in the metformin group,and significantly decreased in the AAT low-dose group and AAT high-dose group.Conclusion The results showed that AAT had obvious hypoglycemic and lipid-lowering effects on type 2 diabetic rats,and low dose of AAT had a tendency to increase the total protein,which could improve the kidney and pancreaticislet morphology in the experimental animals.
引文
[1]Chaudhury A,Duvoor C,Reddy Dendi VS,et al.Clinical review of antidiabetic drugs:implications for type 2 diabetes mellitus management[J].Front Endocrinol(Lausanne),2017,8:6.
[2]Ji Q,Guo C,Xie C,et al.Genetically engineered cell lines forα1-antitrypsin expression[J].Biotechnol Lett,2017,39(10):1471-1476.
[3]Moris D,Chakedis J,Rahnemai-Azar AA,et al.Postoperative abdominal adhesions:clinical significance and advances in prevention and management[J].J Gastrointest Surg,2017,21(10):1713-1722.
[4]Komiyama M,Wada H,Ura S,et al.The effects of weight gain after smoking cessation on atherogenicα1-antitrypsin-low-density lipoprotein[J].Heart Vessels,2015,30(6):734-739.
[5]Ozanne SE,Rahmoune H,Guest PC.Multiplex biomarker approaches in type 2 diabetes mellitus research[J].Methods Mol Biol,2017,1546:37-55.
[6]魏明燕,王国杰,苏虹虹.2型糖尿病患者血糖控制情况与Hb A1c、25-羟维生素D、脂肪代谢的关系[J].中国热带医学,2018,18(2):173-175.Wei MY,Wang GJ,Su HH.Study on relationship between blood glucose control and Hb A1c,25-hydroxyvitamin D and fat metabolism of type 2 diabetes mellitus patients[J].China Tropical Medicine,2018,18(2):173-175.
[7]K?hnlein T,Schmidt-Scherzer K,Greulich T,et al.Expert statement for augmentation therapy in patients with alpha-1antitrypsin deficiency[J].Pneumologie,2014,68(7):492-495.
[8]区洪炎,阮国梅,李志成,等.甘精胰岛素联合二甲双胍治疗初发早期糖尿病肾病的疗效[J].热带医学杂志,2017,17(2):208-210,247.Qu HY,Ruan GM,Li ZC,et al.Insulin glargine combined with metformin in treatment of incipient early diabetic nephropathy[J].J Trop Med,2017,17(2):208-210,247.
[9]张曼,付广真,雷婷.尿液内源性α胰蛋白酶抑制剂重链H4在Ⅱ型糖尿病合并冠心病中的应用[P].中国:CN104714020A,2015-06-17.Zhang M,Fu GZ,Lei T.In the urine of endogenousαtrypsin inhibitor heavy chain H4 Application in type 2 diabetes mellitus with coronary heart disease[P].China:CN104714020A,2015-06-17.
[10]张晓丹,叶剑,廖玉婷,等.人α1-抗胰蛋白酶在胰岛β细胞移植中免疫抑制和保护作用的研究[J].中国病理生理杂志,2013,29(4):619-625.Zhang XD,Ye J,Liao YT,et al.Immunosuppressive and protective effects of humanα1-antitrypsin on pancreaticβ-cell transplantation[J].Chinese Journal of Pathophysiology,2013,29(4):619-625.
[11]Lomas DA,Hurst JR,Gooptu B.Update on alpha-1 antitrypsin deficiency:New therapies[J].J Hepatol,2016,65(2):413-424.
[12]Graterol F,Navarro-Mu?oz M,Ibernon M,et al.Poor histological lesions in Ig A nephropathy may be reflected in blood and urine peptide profiling[J].BMC Nephrol,2013,14:82.
[13]杜任生,庾永基,黄均鹏,等.高危糖尿病人群血清微量元素和脂肪因子的异常变化与血糖水平的相关性[J].热带医学杂志,2017,17(2):183-186.Du RS,Yu YJ,Huang JP,et al.Correlation between abnormal changes of serum trace elements and fatty factors and blood glucose levels in patients with high risk diabetes[J].J Trop Med,2017,17(2):183-186.
[14]Nakahara T,Hyogo H,Yoneda M,et al.Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients[J].J Gastroenterol,2014,49(11):1477-1484.
[15]Sveinsdottir SV,Svensson PJ,Engstr?m G.Inflammatory plasma markers and risk for venous thromboembolism[J].J Thromb Thrombolysis,2014,38(2):190-195.
[16]Eatrides J,Thompson Z,Lee JH,et al.Serum albumin as a stablepredictorofprognosisduringinitial treatment in patients with diffuse large B cell lymphoma[J].Ann Hematol,2015,94(2):357-358.
[17]赵莹,陈顺仪,陈武嘉,等.2型糖尿病患者糖化血红蛋白和凝血功能分析[J].热带医学杂志,2016,16(10):1264-1266,1295.Zhao Y,Chen SY,Chen WJ,et al.Investigations of serum Hb A1c and coagulation function in patients with type 2 diabetes mellitus[J].J Trop Med,2016,16(10):1264-1266,1295.
[18]衣巍伟.α1球蛋白对非小细胞肺癌预后作用的研究[D].济南:山东大学,2015.Yi WW.The prognosis value of percentage composition of serum protein in non-small-cell lung cancer[D].Jinan:Shandong University,2015.
[2]Ji Q,Guo C,Xie C,et al.Genetically engineered cell lines forα1-antitrypsin expression[J].Biotechnol Lett,2017,39(10):1471-1476.
[3]Moris D,Chakedis J,Rahnemai-Azar AA,et al.Postoperative abdominal adhesions:clinical significance and advances in prevention and management[J].J Gastrointest Surg,2017,21(10):1713-1722.
[4]Komiyama M,Wada H,Ura S,et al.The effects of weight gain after smoking cessation on atherogenicα1-antitrypsin-low-density lipoprotein[J].Heart Vessels,2015,30(6):734-739.
[5]Ozanne SE,Rahmoune H,Guest PC.Multiplex biomarker approaches in type 2 diabetes mellitus research[J].Methods Mol Biol,2017,1546:37-55.
[6]魏明燕,王国杰,苏虹虹.2型糖尿病患者血糖控制情况与Hb A1c、25-羟维生素D、脂肪代谢的关系[J].中国热带医学,2018,18(2):173-175.Wei MY,Wang GJ,Su HH.Study on relationship between blood glucose control and Hb A1c,25-hydroxyvitamin D and fat metabolism of type 2 diabetes mellitus patients[J].China Tropical Medicine,2018,18(2):173-175.
[7]K?hnlein T,Schmidt-Scherzer K,Greulich T,et al.Expert statement for augmentation therapy in patients with alpha-1antitrypsin deficiency[J].Pneumologie,2014,68(7):492-495.
[8]区洪炎,阮国梅,李志成,等.甘精胰岛素联合二甲双胍治疗初发早期糖尿病肾病的疗效[J].热带医学杂志,2017,17(2):208-210,247.Qu HY,Ruan GM,Li ZC,et al.Insulin glargine combined with metformin in treatment of incipient early diabetic nephropathy[J].J Trop Med,2017,17(2):208-210,247.
[9]张曼,付广真,雷婷.尿液内源性α胰蛋白酶抑制剂重链H4在Ⅱ型糖尿病合并冠心病中的应用[P].中国:CN104714020A,2015-06-17.Zhang M,Fu GZ,Lei T.In the urine of endogenousαtrypsin inhibitor heavy chain H4 Application in type 2 diabetes mellitus with coronary heart disease[P].China:CN104714020A,2015-06-17.
[10]张晓丹,叶剑,廖玉婷,等.人α1-抗胰蛋白酶在胰岛β细胞移植中免疫抑制和保护作用的研究[J].中国病理生理杂志,2013,29(4):619-625.Zhang XD,Ye J,Liao YT,et al.Immunosuppressive and protective effects of humanα1-antitrypsin on pancreaticβ-cell transplantation[J].Chinese Journal of Pathophysiology,2013,29(4):619-625.
[11]Lomas DA,Hurst JR,Gooptu B.Update on alpha-1 antitrypsin deficiency:New therapies[J].J Hepatol,2016,65(2):413-424.
[12]Graterol F,Navarro-Mu?oz M,Ibernon M,et al.Poor histological lesions in Ig A nephropathy may be reflected in blood and urine peptide profiling[J].BMC Nephrol,2013,14:82.
[13]杜任生,庾永基,黄均鹏,等.高危糖尿病人群血清微量元素和脂肪因子的异常变化与血糖水平的相关性[J].热带医学杂志,2017,17(2):183-186.Du RS,Yu YJ,Huang JP,et al.Correlation between abnormal changes of serum trace elements and fatty factors and blood glucose levels in patients with high risk diabetes[J].J Trop Med,2017,17(2):183-186.
[14]Nakahara T,Hyogo H,Yoneda M,et al.Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients[J].J Gastroenterol,2014,49(11):1477-1484.
[15]Sveinsdottir SV,Svensson PJ,Engstr?m G.Inflammatory plasma markers and risk for venous thromboembolism[J].J Thromb Thrombolysis,2014,38(2):190-195.
[16]Eatrides J,Thompson Z,Lee JH,et al.Serum albumin as a stablepredictorofprognosisduringinitial treatment in patients with diffuse large B cell lymphoma[J].Ann Hematol,2015,94(2):357-358.
[17]赵莹,陈顺仪,陈武嘉,等.2型糖尿病患者糖化血红蛋白和凝血功能分析[J].热带医学杂志,2016,16(10):1264-1266,1295.Zhao Y,Chen SY,Chen WJ,et al.Investigations of serum Hb A1c and coagulation function in patients with type 2 diabetes mellitus[J].J Trop Med,2016,16(10):1264-1266,1295.
[18]衣巍伟.α1球蛋白对非小细胞肺癌预后作用的研究[D].济南:山东大学,2015.Yi WW.The prognosis value of percentage composition of serum protein in non-small-cell lung cancer[D].Jinan:Shandong University,2015.