| Objective:To observe the effect of hirudin on the expression of CTGF and ?-SMA protein in lung tissues of IPF model rats,and to explore the mechanism of hirudin intervention on IPF,providing theoretical basis for the clinical application of hirudin in the treatment of IPF.Method:180 SPF Wistar rats of the same age at the same month were selected,half male and half female,weighing 200±20g,and 18 rats were randomly selected as blank group(K).The remaining 162 Wistar rats were uniformly molded by intratracheal injection of bleomycin.After successful modeling,108 rats were randomly selected model group(M),hormone(J),hirudin in high dose group(G),hirudin dose group(Z),hirudin low-dose group(D)and hirudin dose combined hormone group(what ZJ had),each group of 18.Drug intervention from 2 days after the mold maker,observe and record the general condition of rats,choose three time points in the process of drug(7 d,14 d and 28 d)batch to be put to death in the rat,collecting specimens of lung tissue,macroscopic observation specimens in histomorphology changes,using HE and Masson staining microscopically observed the pathological change,degree of alveolar inflammation and fibrosis,WB method is used to detect IPF model in rat lung tissue protein expression of CTGF,and a-SMA.Result:1.General conditions of rats:The rats in group K were in normal state,in good spirits,in normal diet and drinking water,with acute reaction,smooth fur,good gloss and steady breathing.After modeling,the rats in group M had the worst general condition,which was characterized by listlessness of spirit,cowering on the back of the bow,clustering together,significantly reduced activity,decreased diet and water consumption,rough and dull fur,and rapid breathing.The general state of the rats in the other groups was between the two groups.With the prolonged drug intervention,the mental state,diet and water quantity decreased to different degrees.2.Weight change in rats: compared with group K,the weight of rats in each trea tment group decreased to varying degrees(P<0.01),and the weight loss was the most obvious in the first 3 days,and then gradually recovered.The body weight of group M was the smallest(P<0.01),and the body weight of group ZJ was the same as that of rats in group G(P>0.05),which was significantly greater than that of group Z a nd group D(P<0.01).There was no significant difference between group Z and group D(P>0.05).3.General observation of lung tissue of rats: rats in group K were normal lung tissue with pink color,smooth surface,clear demarcation and good elasticity.The lung tissue of rats in group M was swollen at 7 days,with larger volume and redder color,with spots and patchy stasis spots.At 14 days,there was gray-white solid change,accompanied by scattered hemorrhagic spots and nodular changes.The lower right lung was the most obvious,with decreased lung volume and decreased elasticity.At 28 days,large areas of gray and white areas appeared in the lungs.The texture became hard and the volume was significantly reduced.Compared with group M,all the other groups showed improvement to different degrees,among which ZJ and group G showed the most obvious effect.4.Lung injury score and pulmonary fibrosis score of rats: compared with group K,lung tissue injury and fibrosis score of each treatment group were significantly increased at different stages(P<0.01).Among them,rats in group M were the highest(P<0.01),while those in group ZJ were the lowest(P<0.01),equivalent to group G(P>0.05),and significantly lower than group J,group Z and group D(P>0.05).Group Z was the same as group D(P>0.05),and group J was significantly lower than the previous two groups(P<0.01).5.Results of CTGF protein expression: at different time points,the expression of CTGF protein in group K was the lowest,and the expression in group M was the strongest(P<0.01).The expression of CTGF protein was the weakest(P<0.01)in lung tissues of rats in ZJ group at different time of administration(P<0.01),and the expression in G group and J group was the same(P>0.05),higher than that in ZJ group(P<0.01).The expression of group Z and group D was significantly higher than that of the other groups(P<0.01),and there was no statistically significant difference between the two groups(P>0.05).6.Results of the expression of a-SMA: protein in the K group was the lowest and the a-SMA protein in the M group was the strongest(P<0.01).Each time point to medicine group,the rats to express what Z J group were the weakest(P < 0.01),and group Z D group were obviously higher than that of the rest of the drug group(P < 0.01),and the expression differences between the two groups have no statistical difference(P > 0.05).At 7 and 14 days,the expression of group G and group J was similar(P>0.05),which was inferior to group ZJ(P<0.01).At 28 days,the expression of group G was lower than that of group ZJ,and significantly lower than that of group J(P<0.01).The expression of group J was lower than that of group Z and D(P<0.01).Conclusion:Hirudin can be cut in the lung tissue CTGF,a-SMA protein expression to suppress the IPF formation Fb to MFb phenotype transformation,in the process of reducing the ECM deposition,and promotes its degradation,thus improving the condition of IPF.Hirudin combined with hormone has better therapeutic effect on pulmonary interstitial fibrosis in rats. |
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