| 项标.高血糖对NASH大鼠肝纤维化形成的影响及机制探讨[J].浙江中西医结合杂志,2016,26(5): |
| 高血糖对NASH大鼠肝纤维化形成的影响及机制探讨 |
| Effects of hyperglycemia on the hepatic fibrogenesis in non-alcoholic steatohepatitis rats |
| 投稿时间：2015-10-26 修订日期：2016-02-21 |
| DOI： |
| 中文关键词: 高血糖 非酒精性脂肪性肝炎 肝纤维化 |
| 英文关键词:Hyperglycemia NASH Liver ?brosis |
| 基金项目:浙江省自然科学基金（Y2100826） |
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| 中文摘要: |
| [摘要] 目的 探讨高血糖在非酒精性脂肪性肝炎（NASH）大鼠肝纤维化形成中的作用以及机制。方法 将60只SD大鼠随机数字法分成正常对照组、高血糖模型组、高血糖伴NASH组、氨基胍组和虎杖组，分别检测各组大鼠血糖值，病理学变化（HE染色），纤维化程度，肝组织基质金属蛋白酶组织抑制因子-1（TIMP-1）、转化生长因子-β1（TGF-β1）和晚期糖基化终产物（AGEs）含量的变化及各组大鼠α-平滑肌动蛋白（α-SMA）、结蛋白（desmin）的表达评分。结果 二用药组大鼠的血糖值（14.20±11.74/5.25 ± 0.92，mmol/L）较高血糖组（22.20±1.70，mmol/L）和NASH组（22.21±5.49, mmol/L）降低（均P＜0.05）；高血糖组和NASH组肝组织出现细胞变性和纤维化改变。与NASH组比较，虎杖组肝细胞结构形态较正常，只有较轻度水肿、脂肪变性等炎性改变，未见明显纤维化，α-SMA（4.92 ± 1.69）、Desmin（4.75±1.75）表达及TIMP-1（3473.76 ±372.06，pg/mL）、TGF-β1（125.26 ±28.60 ，ng/mL）、AGEs（75.86±22.36，ng/mL）含量也显著降低（均P＜0.01）。氨基胍组肝组织脂肪变性、水样变性、纤维化程度有所减轻，α-SMA表达增高（9.00 ± 2.04）（P＜0.05），TIMP-1（3543.67±377.05，pg/mL）、AGEs（75.86 ± 22.35，ng/mL）含量降低（均P＜0.01），同时 TGF-β1表达减低（145.31 ± 43.14，ng/mL）但无统计学差异（P＞0.05）。 结论 高血糖可促进NASH大鼠肝纤维化的形成，降低血糖和减少AGEs形成可减轻或抑制肝纤维化的发生；机制之一是激活肝星状细胞。虎杖较氨基胍改善NASH大鼠肝纤维化的作用更明显。 |
| 英文摘要: |
| Aim: To investigate the effects of hyperglycemia on nonalcoholic steatohepatitis mice and the mechanisms underlying these effects.Methods: 60 SD rats were randomly divided into normal control group (10), hyperglycemia group (12),NASH group (14) , aminoguanidine group (12) and giant knotweed group (12). The high glucose rats were copied hyperglycemia-model by streptozotocin(STZ). After oral glucose-lowering drugs intervention, we killed the rats and observed the degree of hepatic steatosis, inflammation, necrosis and fibrosis of liver tissue. At the same time, we detected the expression of α-SMA and Desmin in liver tissues by immunohistochemistry, which are the sign of HSC activation, and tested the fibrosis-relevant factors, like AGEs, TIMP1, TGF-β1by Elisa or Biochemical ways. Results: The blood glucose was lower in 2 intervention group（14.20±11.74/5.25±0.92, mmol/L） than that in hyperglycemia group（22.20±1.70,mmol/L）and NASH group（22.21±5.49, mmol/L）（P＜0.05）. In Giant knotweed group the hepatic tissue displayed a normal form, mild edema, fatty degeneration and inflammatory cell infiltration; hepatic fibrosis was markedly alleviated, expression of α-SMA（4.92±1.69）、Desmin（4.75±1.75）were decreased, and TIMP-1（3473.76±372.06 pg/mL）、TGF-β1（125.26 ± 28.60 ,ng/mL）、AGEs（75.86±22.36 ,pg/mL）levels were declined（P＜0.01）. There was no significant difference between diabetic model group and NASH group. The pathology of hepatic tissue in aminoguanidine group was not improved significantly, but the fatty degeneration, hydropic degeneration, and hepatic fibrosis were slightly alleviated,TIMP-1（3543.67±377.05 ,pg/mL）and AGEs（75.86±22.35, pg/mL）declined in content（P＜0.01）, the expression of α-SMA（9.00±2.04）increased（P＜0.05）, TGF-β1（145.31±43.14 ,ng/mL）expression was reduced, but no statistical difference (P > 0.05).Conclusion: We conclude that high blood sugar can promote the activation of hepatic stellate cells of nonalcoholic fatty liver disease and thereby accelerate liver-?brogenesis in rats, oral glucose-lowering drugs ,such us giant knotweed ,can effectively inhibit stellate cell activation, resulting in alleviation of hepatic fibrosis. |
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