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菩人丹对T2DM胰腺微血管损伤大鼠胰岛茁细胞功能及胰岛素抵抗的影响
刘祖涵1, 张梓倩2
1.北京大学国际医院药剂科, 北京 102206;2.中国医学科学院, 北京协和医学院药物研究所药物代谢室, 北京 100050
摘要:
[目的] 菩人丹超微粉对2型糖尿病(T2DM)胰腺微血管损伤大鼠胰岛β细胞分泌功能的影响,并探讨其作用机制。[方法] 随机选取SPF级雄性Wistar大鼠,采取灌胃自制的脂肪乳结合尾静脉快速注射链脲佐菌素(STZ)30 mg/kg进行模型复制。1周后,将成模大鼠按血糖结合体质量分层随机分为模型组、菩人丹超微粉组(PRD组)、马来酸罗格列酮组和降糖通脉片组,另设同批次雄性Wistar大鼠28只为空白对照组,共5个组。各组分别给予相应药物治疗,每天灌胃1次,正常组及模型组以同比剂量蒸馏水灌胃,均连续灌胃4周。各组均给予普通饲料喂养。4周后,进行口服葡萄糖耐量实验、静脉注射葡萄糖-胰岛素释放实验、葡萄糖-胰岛素曲线下面积比值(FINS-AUC/FBG-AUC)计算、胰岛β细胞功能评估及相关指数评定。[结果] 口服葡萄糖耐量实验中,PRD组血糖在2 h内的降低趋势近似空白对照组,餐后2 h血糖(PG2 h)基本接近糖负荷前的血糖水平[餐后血糖(PG0 h):14.80±1.42;PG2 h:16.17±2.91]。静脉注射葡萄糖-胰岛素释放试验中,PRD组第1时相分泌峰出现在5 min左右,速度相对较快,且胰岛素分泌量较多;第2时相分泌峰出现时间约在30 min左右,基本符合胰岛素短脉冲和长脉冲的分泌模型。PRD组的FINS-AUC/FBG-AUC显著增加(P<0.01)。PRD组胰岛β细胞分泌功能增强,胰岛素分泌增加,胰岛素敏感性提升,胰岛素抵抗性降低。[结论] 菩人丹超微粉可能通过修复脾肾脏腑机能,改善微环境和血流,进而修复胰岛β细胞损伤结构形态和功能,提高胰岛素敏感性,调节糖耐量失常,恢复正常胰岛素双时相分泌。
关键词:  菩人丹超微粉  2型糖尿病  胰腺微血管  胰岛β细胞  胰岛素抵抗
DOI:10.11656/j.issn.1672-1519.2016.07.09
分类号:
基金项目:国家自然科学基金项目(30873249)。
Effect of Purendan on the pancreatic β cell secretion and IR in pancreas micro-circulatory damage in rats with T2DM
LIU Zu-han1, ZHANG Zi-qian2
1.Pharmacy Department, Peking University International Hospital, Beijing 102206, China;2.Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
[Objective] To investigate the effect of Purendan (PRD) supermicro powder on the pancreatic β cell secretion in pancreas micro-circulatory damage in rats with T2DM, and explore the regulation mechanism for PRD in pancreatic β cell secretion.[Methods] Male wistar rats were administered intragastrically with fat milk and STZ and injected intravenously via the lateral caudal vein at a dose of 30 mg/kg. After 1 week, rats were randomly assigned to model group, PRD group, rosiglitazone maleate tablets group, and Jiangtang Tongmai tablet group. The 28 male wistar rats as control were also engaged in the experiment. Treatment were exerted according to grouping principles, and rats in control group and model group were administered intragastrically with the same dose of distilled water for 4 weeks. Then, oral glucose tolerance test, intravenous injection glucose-insulin release test, FINS-AUC/FBG-AUC, pancreatic β cell functional assessment and index of correlation were analyzed.[Results] In oral glucose tolerance test experiment, blood glucose in PRD group rats decreased within 2 h and was close to normal control, PG2 h approximated to plasma glucose level before given oral glucose[PG0 h:(14.80±1.42);PG2 h:(16.17±2.91) mmol/L]. In intravenous injection glucose-insulin release test, the significant secretion peak at the first phase were observed after 5 min in PRD treatment group, beside, secretion peak at the second phase were observed after 30 min, which conform to rapid and long pulsatile insulin secretion fashion. PRD significantly increased FINS-AUC/FBG-AUC(P<0.01). Meanwhile pancreatic β cell secretion were up-regulated, insulin secretion and sensitivity increased, and insulin resistivity decreased in PRD treatment group.[Conclusion] PRD supermicro powder possibly imporved glucose tolerance and insulin secretion in both phase via recovery of pancreatic β cell damage.
Key words:  Purendan supermicro powder  T2DM  pancreas micro-circulatory  pancreatic β cell  insulin resistance
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