| Objective Different concentrations of Pirfenidone(PFD)were used for trabeculectomy in rabbit eyes.To investigate whether it can be applied to inhibit the formation of scars after surgery,the inhibitory effects is concentration-dependent or not,and clarify its possible mechanism by the means of postoperative intraocular pressure(IOP)measuring,survival of functional filtering blebs and ocular side effects observing,expression of TGF-?1 and its related ?-SMA,Collagen I and PCNA in filtering passage comparing.Methods Forty weight of 2.0 to 2.5 kg healthy adult rabbits(40 eyes)were selected,male or female were randomly divided into five groups,one control group and four experimental groups,each with 8 rabbits(8 eyes).Trabeculectomy on right eyes was performed measuring after ocular basal intraocular pressure,and once / day after surgery,avoiding the surgical area for 7 consecutive days.The subconjunctival injection concentration of each experimental group was 1.0g / L,3.0g / L,5.0g / L,10.0g / L PFD 0.1m L,the control group was injected with 0.1m L sterile water it the same place.The intraocular pressure(mm Hg)was measured with a Schiotz tonometer on days 1,7,14,21,and 28 after surgery,and the survival of functional filter vesicles was recorded to observe the ocular side effects.Four groups of experimental animals(4 eyes)were randomly selected and sacrificed by air embolization at 14 and 28 days after operation.The tissues around the eyes were separated,the eyeballs were completely removed,and the filtering passages were used to make pathological specimens.HE staining and immunohistochemical detection The expression of fibrosis and TGF-?1,?-SMA,PCNA and Collagen I in the filter area at each timepoint compared with the control group.All data were statistically analyzed using spss26.0.Results(1)The IOP in the PFD group was 3.0 g / L,5.0 g / L,10.0 g / L at 7,14,21,and 28 days after surgery.The IOP in the PFD group was significantly lower than that in the control group.0.05),and the IOP of the PFD group at a concentration of 1.0 g /L was significantly different from that of the control group on 7 days after surgery only.(P <0.05).(2)There was no difference between the experimental group and the control group in the number of cases of mild anterior chamber flash and mild conjunctiva congestion with a small amount of secretion,and all of them disappeared within 7 days after the operation.No leakage of filtration bubble,lens opacity,corneal edema and other ocular damage were found in each group.(3)Functional filtering bleb formation rate between groups were no difference 1 day after surgery,7,14,21,28 days after the experimental group(3.0 g/L,5.0 g/L,10.0 g/L PFD)group than control group in filtering bleb formation rate difference had statistical significance(P< 0.05),the experimental group 1.0 g/L PFD than the control group only seven days after surgery to reduce difference was statistically significant(P < 0.05),the control group and experimental group(PFD)1.0 / L respectively,21 and 28 days after the functional filtering bleb formation rate is(4)The number of fibroblasts observed at 14 days and 28 days after HE staining.The number of fibroblasts composed of 3.0g / L,5.0g / L,10.0g / L PFD was less than that of the control group and 1.0g / L PFD group.Statistical significance,but there was no significant difference in the number of fibroblasts between 1.0 g / L and the control(P> 0.05).(5)Positive expressions of TGF-?1,?-SMA,Collagen I and PCNA in the filter zone of PFD group at 3.0g / L,5.0g / L,and 10.0g / L at 14,28 days after immunohistochemical staining were higher than those in the control group.The difference was less between the 1.0g / LPFD group and the difference(P <0.05).The expression of each factor in the 5.0g / LPFD group at 10.0g / L PFD filtration zone was not significantly different after 14 days(P>0.05),but the positive expression in both groups was less than that in the 3.0PFDgroup(P <0.05).The positive expression of filtered area increased after 28 days,and the positive expression decreased,and the difference was statistically significant(P<0.05).Conclusion(1)3.0g / L,5.0g / L,10.0g / L PFD has anti-scarring effect and small toxic and side effects after rabbit eye filtration.1.0g / L PFD has reducing IOP and anti-proliferation effects.The effect but the maintenance time is short.According to the results of this experiment,the effective concentration of PFD after filtration is3.0g / L,but the optimal concentration needs to be further studied.(2)PFD can inhibit the proliferation of rabbit fibroblasts,myofibroblasts,and type I collagen fibers by inhibiting the expression of TGF-?1 and its regulated ?-SMA,Collagen I,and PCNA,thereby reducing the proliferation of type I collagen fibers.It even inhibited scarring of the filter tract after surgery,and the inhibitory effect was concentration-dependent. |
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