胱胺酸對人類微小病毒B19非結構蛋白NS1所引發之肝臟傷害的保護效益

人類微小病毒B19感染已知會誘發宿主細胞凋亡和造成肝臟受損。過去文獻指出胱胺酸 (Cystamine) 可防止細胞凋亡及被證實也能減緩小鼠肝臟損傷現象。由於我們實驗室先前研究發現人類微小病毒B19非結構蛋白 (B19-NS1)可藉由細胞凋亡進而導致自體免疫發生及可加重小鼠肝臟損傷。因此，我們想要研究胱胺酸是否也能改善由人類微小病毒B19非結構蛋白B19-NS1所引起的BALB/c小鼠肝臟損傷。本研究利用B19-NS1 BALB/c小鼠作為研究對象，連續14天以腹腔方式注射100uM/mL Cystamine。然後利用明膠蛋白酵素電泳法 (Gelatin zymography) 及西方墨點分析法 (Western blotting, WB) 進行B19-NS1 BALB/c小鼠肝臟發炎反應蛋白表現分析。結果發現，胱胺酸可以減少由B19-NS1引起BALB/c小鼠肝臟中的MMP-9 / MMP-2酵素活性與p38、ERK、JNK和IKKα、IκB與NF-κB (p65) 磷酸化蛋白表現。此外，也可以減少由B19-NS1引起BALB/c小鼠肝臟中的MMP-9、CRP、IL-1β、IL-6與TNF-α等發炎指標蛋白的表現。由這些實驗結果顯示胱胺酸對B19-NS1所引起肝臟損傷具有保護的效果。

Human Parvovirus B19 (B19) infection is known to induce apoptosis and liver dysfunction. Cystamine is indicated in preventing apoptosis and it has been demonstrated to be beneficial on attenuating the hepatic injury in mice. Since our previous study demonstrated that B19-NS1 in development of autoimmunity by inducing apoptosis and aggravates liver injury, we herein intend to investigate the effect of cystamine on B19-NS1 induced hepatic iniury in BALB/c mice. For cystamine treatment, B19-NS1 BALB/c mice were injected intraperitoneally (i.p.) with cystamine daily for 14 days. Immunoblotting assay was performed to examine the signaling of inflammation in liver from B19-NS1 BALB/c mice given cystamine. Significant reduction of hepatic MMP-9 / MMP-2 activity ratio and decreased phosphorylation of p38, ERK, JNK, IKK-α, IκB and NF-κB (p-p65) proteins were observed in livers from B19-NS1 BALB/c mice given cystamine. Additionally, inflammation associated proteins, including MMP-9, CRP, IL-1β, IL-6 and TNF-α, were significantly decreased in the livers of B19-NS1 BALB/c mice given cystamine. Altogether, these results indicate that Cystamine has the protective effects against human parvovirus B19-NS1 induced hepatic injury.