Suppression of p38 mitogen-activated protein kinases inhibitor on myofibroblasts transdifferentiation and extracellular matrix synthesis after filtration surgery in rabbit eyes / 中华实验眼科杂志

ABSTRACT

Background The main cause of filtering surgery failure is over proliferation of fibroblasts in filtering channels,leading to excessive fibrosis and scar formation.Researches determined that p38 mitogen-activated protein kinase(MAPK) signaling pathway plays an important role in fibroblast phenotype transition. Objective The present study was to investigate the inhibitory effect of p38 MAPK inhibitor on myofibroblasts transdifferentiation and the extracellular matrix synthesis after filtration surgery in rabbit eyes. Methods Trabeculectomy was performed on 24 eyes of 12 clean New Zealand white rabbits to establish the filtering operative models.The models were randomized into model group,SB203580 group and mitomycin C ( MMC ) group.1 ml SB203580 ( 0.2 g/L) was conjunctively injected at the end of operation in the rabbits of the SB203580 group,and the cotton piece with 0.2 g/L MMC solution was placed on the operative area for 3 minutes intraoperatively in the rabbits of the MMC group.The bleb appearances were examined under the slit lamp microscope,and intraocular pressure(IOP) was measured with Icare tonometer I,3,7,10,14 days after operation.0.2 ml aqueous humor was extracted and the conjunctive tissue at the filtering area was obtained 14 days after operation for the detection of α-smooth muscle actin (α-SMA) and fibronectin protein by ELISA.Expression of ACTA2 mRNA,connective tissue growth factor(CTGF) mRNA and alpha2 chain of type Ⅰ collagen( COL1A2 )mRNA in conjunctive tissue was assayed with fluorescence real-time PCR. Results Vascularization of fibrosis of filtering bleb were obvious in the eyes of the model group,and the bleb was flat and diffuse in the eyes of the SB203580 group and MMC group on 14 days following operation.No significant difference was seen in IOP before trabeculectomy among these three groups( F=0.065,P=0.937 ).IOP was gradually elevated with the increase of time after operation ( F =32.873,P =0.030 ).ELISA assay showed that α-SMA level in conjunctiva was lower in the SB203580 group and MMC group compared with the model group,and that of MMC group was significant lower than the SB203580 group( P＜0.05 ).Fibronectin level in conjunctiva was lower in the SB203580 group and MMC group compared with the model group,and that of MMC group was significant lower than the SB203580 group (P＜0.05).Fluorescence real-time PCR showed that expressions of the ACTA2 mRNA,CTGF mRNA and COL1A2 mRNA were significantly different among the three groups( P＜0.01 ),with the highest expression in model group and the lowest expression in the MMC group ( P ＜ 0.05 ). Conclusions Fibrotic reaction after trabeculectomy can be suppressed by inhibiting p38 MAPK signal pathway.The mechanism of SB203580 is to reduce the synthesis of myofibroblasts transdiffercntiation and extracellular matrix.