Effects of interleukin-10 on activation and apoptosis of hepatic stellate cells in fibrotic rat live

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:asjdkajsk
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AIM:To study the effects of interleukin-10(IL-10)on the expression of α-smooth muscle actin(α-SMA),nuclear factor-κB(NF-κB)and Fas/Fas ligand(FasL)inhepatic stellate cells of experimental rats with hepaticfibrosis.METHODS:Sixty clean SD rats were randomly dividedinto control group(group N),liver fibrotic group(groupC)and IL-10 treatment group(group I).Control groupreceived intraperitoneal injection of saline(2ml·kg~(-1)),twicea week.Fibrotic group was injected intraperitoneallywith 50% carbon tetrachloride(CCl_4)(2 ml·kg~(-1)),twicea week.IL-10 treatment group was given IL-10 at adose of 4 μg·kg~(-1)20 minutes before CCl_4 administrationfrom the third week.Hepatic stellate cells(HSCs)wereisolated from these rats at the seventh and eleventhweeks during the course of liver fibrosis,respectively.The expression of α-SMA and NF-κB in HSCs wasmeasured by S-P immunohistochemistry.The expressionof Fas and FasL mRNA was measured by RT-PCR.Furthermore,liver tissues were harvested from threegroups at the same time.RESULTS:The CCl_4- induced experimental rat hepaticfibrosis model was established successfully.The purityof extracted hepatic stellate cells was about 95% andthe yield of hepatic stellate cells was 1.2-2.3×10~6/g livertissue averagely.The positive expression of α-SMA andNF-κB was 36.5% and 28.5% respectively in group N.The positive levels of α-SMA and NF-κB were increasedsignificantly in group C compared to group N(P<0.01).The positive signals decreased significantly(P<0.05)ingroup I.In the 11~(th)week,the HSCs of group I becameround with visible pyknotic nuclei.The expression ofNF-μB in group C was significantly increased in a time-dependentmanner(P<0.01),but there was no difference in the α-SMA expression(P>0.05).The mRNA of Fasand FasL in group C was significantly increased in a time-dependent manner compared to that in control group.After treated with IL-10,the expression level of Fas andFasL was higher in group I than in group C.CONCLUSION:The positive expression of α-SMA andNF-κB in hepatic stellate cells is decreased by ectogenicIL-10 in liver fibrosis induced by CCl_4.The expression ofFas and FasL is increased in the course of liver fibrosis,and is further increased by IL-10.IL-10 could inhibitthe activation of HSCs and cause apoptosis of activatedHSCs. AIM: To study the effects of interleukin-10 (IL-10) on the expression of α-smooth muscle actin (α-SMA), nuclear factor- κB (NF- κB) and Fas / Fas ligand of experimental rats with hepatic fibrosis.METHODS: Sixty clean SD rats were randomly dividedinto control group (group N), liver fibrotic group (groupC) and IL-10 treatment group (group I). Control groupreceived intraperitoneal injection of saline (2ml · kg ~ (-1)) twice a week. Fibrotic group was injected intraperitoneally with 50% carbon tetrachloride (2 ml · kg -1) twice a week. IL-10 treatment group was given IL-10 at adose of 4 kg · (-1) 20 minutes before CCl_4 administration from the third week. Hepatatic stellate cells (HSCs) wereisolated from these rats at the seventh and eleventh weeks in the course of liver fibrosis, respectively. The expression of α-SMA and NF- κB in HSCs wasmeasured by SP immunohistochemistry. The expression of Fas and FasL mRNA was measured by RT-PCR. Future and liver tissues were harvested from Three groups at the same time .RESULTS: The CCl 4-induced experimental rat hepatic fibrosis model was established successfully. The purity of extracted hepatic stellate cells was about 95% and the yield of hepatic stellate cells was 1.2-2.3 x 10 ~ 6 / g livertissue averagely. Positive expression of α-SMA and NF-κB were 36.5% and 28.5% respectively in group N. The positive levels of α-SMA and NF-κB were increased significantly in group C compared to group N (P <0.01). The positive signals of α-SMA and NF- (P <0.05) ingroup I. In the 11th (th) week, the HSCs of group I becameround with visible pyknotic nuclei.The expression of NF-μB in group C was significantly increased in a time-dependentmanner (P <0.01) , but there was no difference in the α-SMA expression (P> 0.05) .The mRNA of FasL in group C was significantly increased in a time-dependent manner compared to that in control group. After treatment with IL-10, the expression level of Fas and FasL was higher in group I than in group C.CONCLUSION: The p ositive expression of α-SMA and NF-κB in hepatic stellate cells is decreased by ectogenic IL-10 in liver fibrosis induced by CCl_4. The expression of Fas and FasL is increased in the course of liver fibrosis, and is further increased by IL-10.IL- 10 could inhibit the activation of HSCs and cause apoptosis of activated HSCs.
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