奥曲肽抑制肝星状细胞增殖及细胞外基质合成

Octreotide inhibits proliferation and extracellular matrix synthesis in hepatic stellate cells

目的 :探讨奥曲肽对肝星状细胞 (HSC)增殖与细胞外基质 (ECM)合成的影响。方法 :采用胶原酶二步原位灌注法分离、培养大鼠HSC ,并分别给予转化生长因子 1(TGFβ1) (2 5 μg·L-1)、奥曲肽 (Oct) (0 0 1- 10μg·L-1)或TGFβ1(2 5 μg·L-1) +Oct (0 0 1- 10mg·L-1)干预 ,分别用MTT法、[3 H]-TdR和 [3 H]-脯氨酸掺入法及放射免疫法检测各处理组HSC增殖及ECM合成水平。结果 :Oct能不同程度抑制HSC [3 H]-TdR掺入和增殖 ;能够显著抑制体外培养HSC [3 H]-脯氨酸掺入 ,降低上清液透明质酸 (HA)、层粘连蛋白 (LN)和IV型胶原 (CIV)水平 ;TGFβ1能够诱导HSC表达ECM上调 ,Oct能够阻断TGFβ1对HSC的调控作用。 结论 :Oct能够有效地抑制HSC增殖及ECM合成与分泌。

AIM: To investigate the effects of octreotide (Oct) on the proliferation and extracellular matrix (ECM) synthesis in hepatic stellate cells (HSCs). METHODS: HSCs were isolated from normal male Sprague-Dawley rat liver by a combination of pronase-collagenase perfusion and density gradient centrifugation. The concentration of 2.5 μg/L transforming growth factor β1 (TGFβ1) was used in all the experiment settings. Oct at concentrations of 0.01 mg/L ,0.1 mg/L,1 mg/L and 10 mg/L,respectively,or 0.01 mg/L Oct + TGFβ1,0.1 mg/L Oct+TGFβ1,1 mg/L Oct+TGFβ1,10 mg/L Oct+TGFβ1 were respectively added to the cultured HSCs. Effects of Oct on HSC proliferation and ECM synthesis were respectively determined by MTT method,-TdR and -proline incorporation,or radioimmunoassay. RESULTS: Oct inhibited MTT intake by cultured hepatic stellate cells and down-regulated -TdR incorporation,compared with control group. The concentrations of hyaluronic acid,laminin,collagen type IV in the culture supernatant and -proline incorporation in HSCs were decreased by Oct. TGFβ1 obviously up-regulated proliferation and ECM synthesis in cultured HSCs,and Oct significantly blocked these actions. CONCLUSION: Oct inhibited proliferation and ECM synthesis in cultured HSCs,and elicited the effects of anti-hepatofibrogenesis.