The Effect Of Liraglutide On Renal Fibrosis In Diabetic Rats And On Apoptosis Of Renal Tubular Epithelial Cells Induced By High Glucose

Objective:To observe the effect of liraglutide on blood glucose,lipd and related indexes in rats with type 2 diabetes mellitus.The effects of the activation protein kinase P38?P38MAPK?on the renal mitogen;To investigate the effects of renal tubular epithelial cell apoptosis in high-sugar environment and explore the possible mechanism of renal fibrosis.Methods:?1?In vivo:40 male SD rats,random sampling nine big mice as normal control group?NC group?,the rest of the rats with high sugar and high fat feed and urea by intraperitoneal injection of chain with cephalosporins?STZ?induced by type 2 diabetes model.The rats'fasting blood glucose was more than 11.1 mmol/L as the model success,and then randomly divided into the diabetic rats model group?DM?,the liraglutide treatment group?Lia group?,and the schalletin treatment group?Sax group?.The normal control group and the diabetes model group were given regular intraperitoneal injection of saline,and the drug groups were given corresponding drugs regularly for 6 weeks.Then,the abdominal aortic blood was collected,and serum lipid level,HbA1c level,serum creatinine?Scr?and urea nitrogen?BUN?level were detected in rats.HE staining was used to observe the renal pathological damage in rats.The changes of collagen fibrosis in rat kidney tissue were detected by Masson method.Measurement of collagen volume fraction?CVF,%?;Real-time PCR was used to detect the expression of P38MAPK,transformation growth factor?TGF-?₁?,monocyte chemotactic protein-1?MCP-1?m RNA.In vitro experiment:renal tubular epithelial cells?NRK52E?were selected as target cells,and rats were divided into six groups:normal control group?NC,HG5.6mmol/L?;High sugar group?HG,HG 40mmol/L?;High sugar+liraglutide low-dose group?HG+low Lia,HG 40mmol/L+Lia 1nmol/L?;High sugar+liraglutide-middle dose group?HG+middle Lia,HG 40mmol/L+Lia 10 nmol/L?;High sugar+liraglutide high-dose group?HG+high Lia,HG 40mmol/L+Lia 100 nmol/L?;High sugar+saxagliptin group?HG+Sax,HG 40 mmol/L+Sax 1?mol/L?.CCK8 method was used to detect cell proliferation status,and flow cytometry was used to detect cell apoptosis.The expression of P38MAPK,TGF-?₁ and MCP-1 protein were detected by the western blot method.Results:?1?In vivo:compared with normal control rats,diabetic model group rats high-density lipoprotein cholesterol?HDL-C?decreased significantly?p<0.01?,HbA1c,LDL-C,TG,TC significantly increased?p<0.01 or p<0.05?,Scr and BUN levels rised;HE staining results showed that compared with normal control group,diabetic model group rats kidney tissue cells arranged disorder,swelling deformation,bubbles appear empty,renal tubular atrophy sample changes,has obvious pathological damage sample change;The kidney slices were stained by Masson,and collagen fibrous deposition appeared in the renal interstitial.Western blot results showed that the contents of P38MAPK,TGF-?₁and MCP-1 protein in the diabetes group were all increased in different degrees?p<0.01or p<0.05?.Real Time-PCR test showed that the expression of P38MAPK,TGF-?₁ and MCP-1 m RNA in diabetes group was increased?p<0.01 or p<0.05?.Compared with diabetic model group rats,the liraglutide and saxagliptin drug group rats serum HDL-C increased?p<0.05?,HbA1c,TG,TC,LDL-C have varying degrees of decline?p<0.01 or p<0.05?,Scr and BUN were significantly reduced;HE staining showed that the rational lesion of renal disease was reduced in rats with liraglutide,and there was a significant reduction in the treatment group.Masson staining showed that there was a decrease in the deposition of collagen fibers in the liraglutide group and the group of saxagliptin group,and the CVF?p<0.01?was significantly reduced.Real Time-PCR showed that the expression of P38MAPK,TGF-?₁ and MCP-1mRNA in each group was decreased?p<0.01 or p<0.05?.?2?In vitro experiment:Compared with normal group of cell proliferation,cell proliferation by high sugar group is relatively obvious inhibition,apoptosis rate increased significantly,the amount protein expression of P38MAPK,TGF-?₁ and MCP-1 was increased obviously;After added with different doses of liraglutide drugs,each cell proliferation inhibition situation eased,apoptosis rate is reduced,and within a certain range,with the increase of liraglutide dose,the effect became more and more obvious.Conclusions:?1?The liraglutide of high sugar and high fat+STZ induced diabetic model rats with improved high blood glucose and lipid metabolism disorders,and can increase the weight of the diabetic model rats,improve the general condition of rats.?2?Liraglutide can reduce the content of P38MAPK,TGF-?₁ and MCP-1 in renal tissues,and improve renal fibrosis in diabetic rats.?3?Liraglutide may improve the apoptosis of renal tubular epithelial cells induced by high glucose,and its mechanism may be related to down-regulation of expression of P38MAPK,TGF-?₁ and MCP-1.