高氧通过上调转化生长因子-β的表达加速肝纤维化进展。
Hyperoxia accelerates progression of hepatic fibrosis by up-regulation of transforming growth factor-β expression.
作者信息
Lee Sang Hwa, Do Sung-Im, Kim Hyun-Soo
机构信息
Sang Hwa Lee, Hyun-Soo Kim, Department of Pathology, Aerospace Medicine Research Center, Aerospace Medical Center, Republic of Korea Air Force, Chungcheongbuk-do 363-849, South Korea.
出版信息
World J Gastroenterol. 2014 Mar 21;20(11):3011-7. doi: 10.3748/wjg.v20.i11.3011.
AIM
To investigate the effect of hypoxia or hyperoxia on the progression of hepatic fibrosis and to examine the role of transforming growth factor-β (TGF-β) in the livers of rats exposed to hypoxic or hyperoxic conditions.
METHODS
Male Sprague-Dawley rats were injected intraperitoneally with thioacetamide to induce hepatic fibrosis and were randomly divided into a hypoxia group, a hyperoxia group and an untreated control group. Ten rats in the hypoxia group were exposed to an altitude of 20000 ft for 1 h/d during 7 wk. Ten rats in the hyperoxia group were exposed to a water depth of 20 m with 100% oxygen supply for 1 h/d during 7 wk. We evaluated the degree of hepatic fibrosis using Masson trichrome stain and examined the expression level of hepatic TGF-β mRNA using quantitative real-time reverse transcriptase-polymerase chain reaction analysis.
RESULTS
Eight of 10 rats exposed to hypoxia showed diffuse and confluent fibrosis with the formation of structurally abnormal parenchymal nodules involving the entire liver, consistent with hepatic cirrhosis. Nine of 10 rats exposed to hyperoxia also demonstrated obvious histological findings of hepatic cirrhosis identical to those in hypoxic rat livers. In contrast, 8 of 10 untreated rats had periportal or septal fibrosis only. The frequency of hepatic cirrhosis in hypoxic rats (P = 0.009) and hyperoxic rats (P = 0.003) was significantly higher than that in untreated rats. In addition, hepatic TGF-β mRNA levels in hyperoxic rats were significantly higher than those in untreated rats. The mean value of the normalized TGF-β mRNA/β-actin expression ratio in the hyperoxic rats was 1.9-fold higher than that in the untreated rats (P = 0.027).
CONCLUSION
We demonstrated that both hypoxia and hyperoxia accelerated the progression of hepatic fibrosis in rats. Significant up-regulation of hepatic TGF-β in hyperoxic rats suggests that TGF-β is involved in the acceleration of hepatic fibrosis under hyperoxic conditions.
目的
研究缺氧或高氧对肝纤维化进展的影响，并探讨转化生长因子-β（TGF-β）在缺氧或高氧条件下大鼠肝脏中的作用。
方法
雄性Sprague-Dawley大鼠腹腔注射硫代乙酰胺诱导肝纤维化，随机分为缺氧组、高氧组和未处理对照组。缺氧组10只大鼠在7周内每天暴露于20000英尺海拔高度1小时。高氧组10只大鼠在7周内每天暴露于20米水深并给予100%氧气供应1小时。我们使用Masson三色染色评估肝纤维化程度，并使用定量实时逆转录聚合酶链反应分析检测肝脏TGF-β mRNA的表达水平。
结果
10只暴露于缺氧环境的大鼠中有8只表现出弥漫性和融合性纤维化，形成结构异常的实质结节，累及整个肝脏，符合肝硬化表现。10只暴露于高氧环境的大鼠中有9只也表现出与缺氧大鼠肝脏相同的明显肝硬化组织学表现。相比之下，10只未处理的大鼠中有8只仅有门周或间隔纤维化。缺氧大鼠（P = 0.009）和高氧大鼠（P = 0.003）的肝硬化发生率显著高于未处理大鼠。此外，高氧大鼠肝脏TGF-β mRNA水平显著高于未处理大鼠。高氧大鼠中标准化的TGF-β mRNA/β-肌动蛋白表达比值的平均值比未处理大鼠高1.9倍（P = 0.027）。
结论
我们证明缺氧和高氧均加速了大鼠肝纤维化的进展。高氧大鼠肝脏TGF-β的显著上调表明TGF-β参与了高氧条件下肝纤维化的加速过程。
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