【摘要】 目的 探討丙型肝炎病毒非結構蛋白NS4B對肝細胞內p53表達的影響，以及在肝癌發生中的作用與機制。 方法 設置空白對照組、空白載體組、轉染NS4B組、轉染p53組、共轉染NS4B及p53組。使用脂質體介導轉染法，轉染丙型肝炎病毒非結構蛋白重組質粒PCXN2-NS4B及突變型p53基因重組質粒pC53-CX22AN3進入Chang肝細胞內，并用G418篩選獲得穩定表達細胞。采用免疫細胞化學法檢測p53表達率。 結果 空白對照組無p53表達，空白載體組及轉染NS4B組呈弱陽性表達，轉染p53組及共轉染組呈陽性表達；轉染p53組、共轉染組分別與空白對照組、空白載體組及轉染NS4B組比較，差異均有統計學意義 （Plt;0.05）。 結論 NS4B可能抑制p53表達，也可能阻止其進入細胞核，但NS4B與突變型p53關系不明確。NS4B導致肝細胞異常增生，誘導肝癌發生可能不依賴p53的異常表達及突變。【Abstract】 Objective To investigate the effect of hepatitis C Virus on-structural protein 4B(HCV NS4B) on expression of p53 in hepatic cell, and to study the role and mechanism in development of hepatocellular carcinoma. Methods The experiment was divided into negative control, pure vector PCXN2, PCXN2-NS4B, PC53-cx22AN3, and co-transfection group. Recombinant plasmid PCXN2-NS4B and mutant p53 gene--PC53-cx22AN3, PC53-cx22AN3 with PCXN2-NS4B, blank vectors were transfected into Chang liver cell by liposome-mediated transfection respectively. Positive cells were screened by G418. The expression rate of p53 was measured by immunocytochemistry. Result No expression rate of p53 gene in control group was found, lower positive expression in group PCXN2 and PCXN2-NS4B. The expression of p53 gene in group PC53-CX22AN3 and co-transfection was ber than the others (Plt;0.005). Conclusion HCV-NS4B may inhibit the expression of p53 gene, and it may play a crucial role in inhibiting p53 transfered to hepatic cells nuclear. But it isn’t clear that the. HCV-NS4B can enhance the role of mutant p53 gene. It suggested that HCV-NS4B induce proliferation of hepatic cell not through regulating the expression of p53.
【摘要】 目的 探討慢性丙型肝炎患者干擾素治療前后血清自身抗體的合并狀況。 方法 回顧性分析2005年2月-2008年2月66例慢性丙型肝炎患者應用干擾素治療前后的檢測結果，觀察治療前后自身抗體合并狀況及與干擾素療效的關系。 結果 ①66例慢性丙型肝炎患者中39例自身抗體陽性，陽性率59.1%（39/66），主要為ANA；②自身抗體的產生與年齡相關，而與性別、HCVRNA定量無關；③自身抗體陽性組干擾素應答率66.7% （26/39）明顯高于陰性組40.7%（11/27），二者比較差異有統計學意義；④干擾素治療后，自身抗體陰性組自身抗體檢出率為44.4%（12/27），但滴度均lt;1∶320；治療前抗甲狀腺球蛋白抗體陽性患者會出現較高的甲狀腺功能異常率。 結論 慢性丙型肝炎合并血清自身抗體陽性的患者干擾素應答率高于陰性組，但應注意抗甲狀腺球蛋白抗體，以預測不良反應。【Abstract】 Objective To explore the consolidation of serum autoantibodies in chronic hepatitis C patients treated with interferon. Methods The clinical data of 66 patients with chronic hepatitis C treated with interferon from February 2005 to February 2008 were retrospectively analyzed. The relationship between the consolidation of serum autoantibodies and the effect of interferon was observed. Results ①There were 39 patients with positive autoantibodies; the positive rate was 59.1% (39/66) and ANA was the main antibody. ②The appearance of autoantibodies correlated with the patients′ ages but not with the sexes and CVRNA quantification. ③The interferon response rate in autoantibodies positive group was 66.7% (26/39) which was much higher than that in the negative group; the difference between the two groups was significant. ④After the interferon treatment, the autoantibody detection rate in autoantibody negative group was 44.4%(12/27)and the titer was lower than 1:320; before the treatment, the anti-thyroglobulin antibody-positive patients had a higher rate of thyroid dysfunction. Conclusion The interferon response rate in chronic hepatitis C patients with positive serum autoantibodies is higher than that in the patients with negative serum autoantibodies. Anti-thyroglobulin antibodies should be noted to predict the adverse effects.
