糖尿病大鼠胰腺泡组织中ERK5的表达及意义

High expression of ERK5 in pancreatic acinus of diabetic rats and its significance

目的研究大丝裂酶原激活蛋白激酶(bigMAPkinase1,BMK1/ERK5)在糖尿病大鼠胰腺泡组织血管上的表达水平及意义。方法20只SD大鼠按随机数字表法分成对照组(n=10)和糖尿病组(n=10),采静脉血测其空腹血糖、胰岛素及血脂;取胰腺组织行HE染色病理学观察。糖原染色(PAS)观察血管病变。免疫组化检测胰腺泡组织Ⅰ、Ⅳ型胶原的表达。原位杂交检测血管上ERK5mRNA表达。结果①糖尿病组血管壁明显增厚,血管周围明显炎症细胞浸润,局灶腺泡萎缩,炎症细胞浸润。②糖尿病组血管壁PAS阳性物质沉积。③Ⅳ型胶原主要表达血管基底膜,Ⅰ型胶原主要表达于糖尿病大鼠有腺泡萎缩、炎症浸润的组织部位,糖尿病组较对照组表达增高(P<0.01)。④ERK5mRNA主要在胰腺血管上表达,其表达水平糖尿病组较对照组明显增高(P<0.01)。结论伴有脂代谢障碍的糖尿病大鼠胰腺泡组织中的微循环障碍,可能为ERK5的高表达所致。ERK5的高表达可能是高脂血症患者易发胰腺炎的重要发病基础之一。

Objective To investigate the expression and significance of big mitogen-activated protein kinase 1（BMK1 or ERK5）in the pancreatic acinus of diabetic rats.MethodsTwenty SD rats were randomly divided into normal control group（n=10）and streptozotocin（STZ）-induced diabetic group（n=10）.At the end of 14 weeks inducement,all rats were sacrificed and venous blood and pancreatic tissues were collected.The levels of fasting blood glucose,insulin and blood fat were determined to identify the establishment of diabetic rat model.The specimens of pancreas were fixed and embedded.Hematoxylin-eosin staining was performed to observe the morphological changes.Periodic acid-Schiff（PAS）staining was carried out for the vascular changes.The expressions of type Ⅰ and Ⅳ collagen were determined by inmmunohistochemical method.BMK1/ERK5-mRNA was detected by in situ hybridization.ResultsCompared with the control,in diabetic group the vascular wall was thickening,inflammatory cells were infiltrated in perivascular area,local acinus was atrophy and the expression of type Ⅳ collagen was mainly expressed in vascular basement membrane,while type Ⅰ collagen was in local atrophy acinus tissue with inflammation（P〈0.05）.ERK5 mRNA was expressed in the vascular endothelial cells,and significantly increased in diabetic rats（P〈0.01）.PAS-positive substances were deposited in the vascular wall in diabetic group but were not observed in the control group.ConclusionERK5 may contribute to the microcirculation disturbance in the pancreas of diabetic rats with dyslipidemia,moreover,ERK5 may be one reason for pathogenesis of acute pancreatitis due to hyperlipidemia.