The Effect Of Rapamycin On Expression Of MMP-2 And TIMP-1 In Septic Pulmonary Fibrosis

Objectives:To investigatethe effect of rapamycin on the expression of MMP-2 and TIMP-1 in septic rat pulmonary fibrosis.Methods:90 SD rats were divided into control group?normal saline intraperitoneal injection of 2ml,1hour after intraperitoneal injection of saline solution 2ml?,endotoxin group?LPS5mg/kg dissolved in 2ml by intraperitoneal injection of saline,1hour after intraperitoneal injection of saline solution 2ml?,rapamycin group?LPS5mg/kg dissolved in 2ml by intraperitoneal injection of saline,1hour after rapamycin 2mg/kg dissolved in2ml by intraperitoneal injection of saline solution?,each group is divided into 7,14,21,28and 35 days 5 subgroups,six in each group.The rats were sacrificed on the corresponding days,Masson trichromatic staining was adopted,collagen deposition in lung tissues was observed under light microscope,and HYP content of hydroxyproline in lung tissues was detected.Dynamic changes in expression of?-SMA and TGF-?₁ protein were detected by Western Blot.The expression changes of MMP-2 and TIMP-1 mRNA in lung tissues were detected by Real-time PCR.Results:1.Pulmonary tissue in the endotoxin group initially showed changes of alveolar inflammation,and pulmonary tissue fibrosis gradually appeared after 7 days.Pulmonary alveolitis and pulmonary tissue fibrosis in the rapamycin treatment group were significantly alleviated compared with the endotoxin group.2.There was no significant change in lung Ashcrof score and HYP content in the control group.The endotoxin group increased from day 7 to day 35 compared with the control group,the difference was statistically significant?P<0.05?,and reached the peak on day21.Compared with the endotoxin group,the rapamycin group decreased significantly from day 7 to day 35?P<0.05?.3.Expression of?-SMA and TGF-?₁ in lung tissues of rats in the control group was not significantly altered.On the 7th day,the expression of endotoxin in the group was significantly higher than that in the control group?P<0.05?.It peaked on the 21st day.Compared with the endotoxin group,the rapamycin group was significantly reduced from day 7 to day 35,and the difference was statistically significant?P<0.05?.4.The expression of MMP-2 and TIMP-1 mRNA in the lung tissues of rats in the control group was not obvious.The expression of endotoxin group increased from day 7 to 35,and was higher than that of the control group,the difference was statistically significant?P<0.05?.The expression of MMP-2 mRNA reached a peak on day 21,and that of TIMP-1 mRNA reached a peak onday28,andgradually decreased.Compared with the endotoxin group,the rapamycin group was significantly reduced from day 7 to day 35?P<0.05?.Conclusion:rapamycin can effectively inhibit pulmonary fibrosis caused by sepsis by inhibiting the expression of?-SMA,TGF-?₁,MMP-2,TIMP-1,and thus has a protective effect on pulmonary fibrosis.