The Further Study Of The Mechanism Of GLP-1R Agonist-induced Rat Pancreatic Tissue Lesion

Objective:To explore the mechanism of GLP-IR agonist-induced rat pancreatic tissue lesion.Methods:30SD male rats were divided into three groups acc-ording to the principle of complete random design, each group has10rats, namely GLP-1R agonist experimental group, diabetes-model experimental group and control group. Diabetes-model rats were ind-uced by streptozotocin (STZ,35mg/kg) and high-sugar and high-fat diet. The GLP-1R agonist experimental group and diabetes-mode-1experimental group were subcutaneously administered of GLP-IR agonist respectively in dose5μg/kg each time, twice a day, at8a. m. and6p.m. Animal weights were weighted weekly and the dose-s of GLP-1R agonist were adjusted according to current weight. T-he control group was treated with same amount of saline. After10weeks of treatment all rats were killed and the pancreatic tissues w-ere disposed. ELISA was to measure the amount of matrix metallo protei-nase-2(MMP-2) and matrix metalloproteinase-9(MMP-9) in pan creatictissue, Immunohistochemical was used to test the expression of a-s-mooth muscle actin (a-SMA) and type III collagen protein in pancr-eatic tissue, all specimen were stained with HE.Results:The amount of MMP-2and MMP-9in GLP-IR agonist experimental group and diabetes-model experimental group were significantly higher than the control group, the difference was statistically significant. In the control group, a very small amount of α-SMA and Ⅲ collagen were expressed in the interstitial. However, α-SMA and Ⅲ collagen were expressed in all part of the lesions of GLP-1R agonist experimental group and diabetes-model experimental group. In four cases of diabetes-model experimental group and two cases of GLP-1R agonist experimental group, the expression of α-SMA and Ⅲ collagen were significantly higher than the control group, The difference of α-SMA and Ⅲ collagen in experimental groupand control group were statistically significant. α-SMA and can be only observed in the vessel wall in control group, However, they were also observed in pancreatic acinar cell interstitial, in addition to the vessel wall in the other two groups.Conclusions:Long-term subcutaneous injection of GLP-1R agonist causes the expression of a-smooth muscle actin and Ⅲ collagen protein in pancreatic acinar cell interstitial, the amount of matrix metallopro-teinase-2and matrix metaloproteinase-9in pancreatic acinar cell interstitial were significant increase, inducing change of Pancreatic tissue with acute inflamematory change.