Experimental Research On TNF-α,TGF-β₁ And MMP-9,TIMP-1 In Pulmonary Fibrosis Rats By Xiankekeli

Purposes : To make Pulmonary fibrosis rat models by Bleomycin A5, observe pathomorphism changes in these models and TNF-αin blood and effects on TGF-β1, TGF-β1mRNA, MMP-9 and TIMP-1 in rat model's lungs, and discuss the prevention mechanism of Xiankekeli on Pulmonary fibrosis.Methods: Divide 108 rats into 6 groups at random, which are control group, model group, prednisone group, high dose Xianke group(HD group), medium dose Xianke group(MD group) and low dose Xianke group(LD group), with 18 rats in each group. They were fed with common forage and were made into the models of Pulmonary fibrosis. On the second day after the models were successfully made, the rats in control group and model group were administrated with Nacl, while the rats in prednisone group with prednisone, HD group, MD group and LD group with Xiankekeli 10g/kg, 5g/kg, 2.5g/kg respectively. Then measure TNF-αby ELISA in blood which was taken from rats aortaventralis artery on the 7th day, 14th day, and 28th day respectively; measure Pulmonary fibrosis degrees in the lung dyed with HE and Masson; measure the expression of TGF-β1, MMP-9, TIMP-1 in the lung by immunol histochemistry, and TGF-β1mRNA by RT-PCR.Results:There are significant differences in alveolar catarrh and Pulmonary fibrosis degrees, and in expressions of TNF-α, TGF-β1, TGF-β1mRNA, MMP-9,TIMP-1(p<0.01 or p <0.05)among the model group, prednisone group and 3 Xiankekeli groups.Compared with the model group, there are significant differences in Alveolar catarrh degrees in prednisone group, HD group and MD group on the 7th day(p<0.01 or p<0.05);while the differences are significant in the prednisone group and HD group on the 14th day(p<0.01 or p<0.05), and significant in HD group on the 28th day(p<0.05).There are also prominent differences in Pulmonary fibrosis degrees in prednisone group, HD group and MD group on the 7th day and 14th day compared with the model group(p<0.05 or p<0.01)and significant differences among prednisone group,HD group,MD group and LD group on the 28th day(p<0.05 or p<0.01).The expressions of TNF-α,TGF-β1 in prednisone group, HD group,MD group and LD group are significantly different compared with those in the model group(p<0.01 or p< 0.05). And the expression of TNF-αin MD group has great difference compared with the prednisone group(p<0.05).The expressions of TGF-β1mRNA in prednisone group, HD group and MD group have significant difference on the 7th day(p<0.01 or p<0.05);the same difference among prednisone group, HD group,MD group and LD group compared with the model group on the 14th day(p<0.01 or p<0.05);and significant differences among prednisone group and HD group on the 28th day(p<0.05).The expressions of MMP-9 in prednisone group, HD group and MD group are significantly different on the 7th and 14th day(p<0.01), while significantly different in prednisone group and HD group on the 28th day(p<0.05 or p<0.01).The expressions of TIMP-1 in prednisone group, HD group and MD group have great differences compared with the model group(p<0.01)and significantly different in LD group on the 14th and 28th day compared with the model group(p<0.05 or p<0.01).Conclusions:1. Xiankekeli can alleviate alveolar catarrh and Pulmonary fibrosis degree on Pulmonary fibrosis rats significantly. The function is similar to that of prednisone. It is of great significance to observe the mechanism of Xiankekeli in preventing Pulmonary fibrosis due to the lack of treating methods in clinic at present.2. Xiankekeli HD group can restrain alveolar catarrh and Pulmonary fibrosis degree and this group is better than other dose groups in restraining the expression of TGF-β1,TGF-β1mRNA,MMP-9 and TIMP-1. Hence the Xiankekeli HD is effective in restraining Pulmonary fibrosis, which may be the proper dose in clinic.3. Xiankekeli can relieve alveolar catarrh by restraining the expression of TNF-αin Pulmonary fibrosis rats, and restrain the expressions of TGF-β1,TGF-β1mRNA,MMP-9 and TIMP-1 in Pulmonary fibrosis rats lung, which might be one of the mechanisms in preventing and treating Pulmonary fibrosis.