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目的探讨胃肠转流术对链脲佐菌素(STZ)所致胰岛损伤大鼠的影响并探讨其机制。方法选择SD大鼠30只,随机分为空白对照组、模型组、代谢手术组各10只。代谢手术组行改良Roux-en-Y胃肠转流术,空白对照组、模型组仅做单纯开腹、关腹处理。手术7 d后,模型组、代谢手术组均腹腔注射STZ建立糖尿病模型,空白对照组腹腔注入等量生理盐水。分别于造模前1天、造模后第7、14天时抽取各组大鼠空腹尾静脉血,检测血糖水平。于造模前1天、造模后2 h、造模后第7、14天时抽取空腹尾静脉血,采用ELISA法检测血浆C肽水平,以评价胰岛损伤情况。于造模前1天、造模后24 h、造模后第7天时抽取空腹尾静脉血,采用ELISA法检测血浆TNF-α水平。于造模第2天时取胰腺组织,采用Western blotting法检测凋亡相关蛋白B细胞淋巴瘤-2相关蛋白X(Bax)、B细胞淋巴瘤蛋白-2(Bcl2)、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)表达。结果造模后第7、14天时,模型组血糖高于造模前及同时间点空白对照组,代谢手术组血糖低于模型组(P均<0.01)。造模后第7、14天时,模型组血浆C肽水平均低于造模前及同时点空白对照组,代谢手术组血浆C肽水平均低于模型组(P均<0.01)。造模后24 h及第7天时,模型组血浆TNF-α水平均高于造模前及同时间点空白对照组,代谢手术组血浆TNF-α水平均低于模型组(P均<0.01)。与代谢手术组相比,模型组Bcl2蛋白表达降低,CHOP、Bax蛋白表达增高(P均<0.01)。结论胃肠转流术可减轻STZ导致的大鼠胰腺组织损伤,其机制可能与减轻胰岛细胞的炎症反应、抑制胰岛细胞凋亡有关。
Objective To investigate the effect of gastrointestinal bypass on streptozotocin (STZ) -induced islet injury in rats and its mechanism. Methods Thirty SD rats were randomly divided into blank control group, model group and metabolic surgery group. Metabolic surgery group modified Roux-en-Y gastrointestinal bypass surgery, blank control group, the model group only simple open abdominal surgery. After 7 days of surgery, model group and metabolic surgery group were given intraperitoneal injection of STZ to establish the model of diabetes mellitus. The blank control group was injected intraperitoneally with equal volume of normal saline. One day before model establishment and the 7th and 14th day after model establishment, the fasting tail vein blood of each group was taken and the blood glucose level was measured. Fasting tail vein blood was collected at 1 day before modeling, 2 h after modeling and 7 and 14 days after modeling. Plasma C-peptide levels were measured by ELISA to evaluate the injury of islets. Fasting tail vein blood was collected at 1 day before model establishment, 24 h after model establishment and 7 days after model establishment. Plasma TNF-α level was measured by ELISA. Pancreatic tissues were harvested on the second day of modeling. Western blotting was used to detect the expression of Bax, Bcl-2, C / EBP The response element binds transcription factor homologous protein (CHOP) expression. Results At the 7th and 14th days after modeling, the blood glucose of the model group was higher than that of the blank control group before and at the same time point. The blood glucose of the metabolic surgery group was lower than that of the model group (all P <0.01). At the 7th and 14th days after modeling, the levels of plasma C-peptide in the model group were lower than those in the control group before and at the same time point. The levels of plasma C-peptide in the metabolic surgery group were lower than those in the model group (all P <0.01). At 24 h and 7 d after model establishment, the level of plasma TNF-α in the model group was higher than that in the control group before and at the same time point. The level of plasma TNF-α in the metabolic surgery group was lower than that in the model group (all P <0.01) . Compared with the metabolic surgery group, the expression of Bcl2 and CHOP and Bax in the model group decreased (all P <0.01). Conclusion Gastrointestinal bypass can relieve the pancreatic tissue injury induced by STZ in rats. The mechanism may be related to the reduction of inflammatory response and islet cell apoptosis in islet cells.