| Objective To investigate the expression of PDGF/ERK signaling inexperimental hepatic fibrosis rats treated with TIMP-1,-2and TGF-β1short interference RNA (siRNA).Methods A total of60rats were randomly divided into six groups:model group, negative control group, TIMP-1siRNA treatment group,TIMP-2siRNA treatment group, TGFβ1siRNA treatment group andnormal group. Rats model of hepatic fibrosis were induced by40%CCL4for12weeks. All rats except normal group were hydrodynamic injectedwith0.25mg/Kg TGF-β1, TIMP-1, TIMP-2and control siRNA plasmidrespectively, while the same amount of saline was given to the normalcontrol and model rats. All rats were sacrifced on the12th week and liversamples were obtained for observing the degree of liver fibrosis by HE andsirius red staining. The expression of PDGF/ERK in the liver wasdetermined by quantitative real-time PCR, Western blot andimmunohistochemistry.Result Histological analysis demonstrated that fibrotic levels weresignificantly attenuated in TGFβ1, TIMP-1and-2siRNA groups. The expression of PDGF-BB, PDGFRβ and p-ERK1/2in the model group,negative control group and siRNA groups were markedly higher than thosein normal group（P＜0.05）. In comparison with the model group andnegative control group, the expression of PDGF-BB, PDGFRβ, p-ERK1/2in the TGF-β1and TIMP-1/2siRNA groups were markedlydown-regulated（P＜0.05）. The expression of PDGF-BB and PDGFRβwere not different between TGF-β1and TIMP-1/2siRNA group. However,the expression of p-ERK1/2in the TGF-β1siRNA group were notablyincreased than those in TIMP-1or-2siRNA group.Conclusions TGF-β1, TIMP-1and-2siRNA in vivo can effectivelydownregulate PDGF-BB and PDGFRβ, and expression of p-ERK1/2infibrotic liver, which may contribute to its effect in improving hepaticfibrosis through suppressing the proliferation of HSCs mediated byPDGF/ERK pathways. Moreover, TIMPs seem to be a more potentialanti-fibrogenesis target, for the expression of p-ERK1/2was lower inTIMP-1/2group than in TGFβ1group. |
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