目的 观察菩人丹(PuRenDan)对2型糖尿病胰腺微循环损伤大鼠胰腺组织中血管内皮生长因子(VEGF)及其受体(VEGFR2/p-VEGFR2)和血管生成抑制素(Angiostatin)、内皮细胞抑制素(Endostatin)的影响,探讨菩人丹修复胰腺微循环障碍的机制。方法 通过高脂饲料喂养(12周)与尾静脉快速注射小剂量链脲佐菌素(30mg/kg)的方法建立大鼠模型。在同批次正常大鼠中随机选15只为正常对照组,后将成模大鼠随机分为:模型组、菩人丹组(1.77g/kg)、降糖通脉片组(0.42g/kg)和二甲双胍组(0.14g/kg),每组15只。各组大鼠每天灌胃1次,正常对照组和模型组给予等剂量蒸馏水,连续给药4周后,提取各组大鼠胰腺组织总蛋白质,采用Westernblot法测定各组大鼠胰腺组织中VEGF及其受体VEGFR2的蛋白质表达和磷酸化水平,以及Angiostatin、Endostatin的蛋白质表达水平。结果 与正常对照组相比,模型组胰腺组织VEGF蛋白质表达水平和受体VEGFR2磷酸化水平明显降低(P〈0.01),而Angiostatin、Endostatin蛋白质表达水平显著增高(P〈0.01);菩人丹干预后,VEGF蛋白质表达水平和受体VEGFR2磷酸化水平均显著上调(P〈0.01),而Angiostatin、Endostatin蛋白质表达则被抑制(P〈0.01)。其与阳性对照药降糖通脉片和二甲双胍作用相当。结论 菩人丹通过上调血管生成促进因子VEGF蛋白质表达及其受体VEGFR2磷酸化,抑制血管生成抑制因子Angiostatin、Endostatin的蛋白质表达,促进糖尿病状态下胰腺组织微血管新生,进而改善胰腺微循环障碍,发挥其对胰岛β细胞的保护、修复作用。
Objective To observe the impacts of puren pills on VEGF and its receptor(VEGFR2 / p- VEGFR2),Angiostatin and Endostatin in the rats of pancreas micro - circulatory damage of T2DM so as to explore the mechanism of puren pills for pancreas micro - circulatory disturbance. Methods The feeding with high fat diet(12 weeKs)and the rapid injection with streptozotocin of small dose(30 mg/ Kg)via the vein on the tail were used to establish rat model. Among the normal rats of same batch,15 rats were selected ran-domly to set up a normal control group. The modeled rats were randomized into a model group,a puren pills group(1. 77 g/ Kg),a jiangtang tongmai tablets group(0. 42 g/ Kg)and a metformin group(0. 14 g/ Kg),15 rats in each one. The gavage was given once every day in the rats of each group. The stilled water of same dose was used in the normal control group and the model group. The medication was given continuously for 4 weeKs. Af-terwards,the total protein was collected from pancreas tissue in the rats of each group. Western blot method was adopted to determine the protein expressions of VEGF and VEGFR2 and the level of phosphorylation,as well as the protein expressions of Angiostatin and Endostatin. Results Compared with the normal control group, the protein expression of VEGF in pancreas tissue and the phosphorylation level of VEGFR2 were reduced apparently(P ﹤ 0. 01),and the protein expressions of Angiostatin and Endostatin were increased significantly (P ﹤ 0. 01). After the intervention with puren pills,the protein expression of VEGF in pancreas tissue and the phosphorylation level of VEGFRs were up - regulated significantly(P ﹤ 0. 01)and the protein expressions of Angiostatin and Endostatin were inhibited(P ﹤ 0. 01). The effects were similar to those in the positive con-trol groups treated with jiangtang tongmai tablets and metformin. Conclusion Puren pills up - regulate the protein expression of VEGF in pancreas tissue and the phosphorylation level of