Bauer M, Paquette N C, Zhang J X, Bauer I, Pannen B H, Kleeberger S R, Clemens M G
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
Hepatology. 1995 Nov;22(5):1565-76.
Recent evidence suggests that hepatic stellate cells function as liver-specific pericytes that are highly contractile in response to endothelin-1 (ET-1). Liver injury has been shown to lead to "activation" of stellate cells producing a phenotypic change to a more myofibroblastic cell type including loss of vitamin A and increased contractility. The present study was undertaken to test the effects of short-term chronic ethanol consumption (36% of total calories for 5 weeks according to the Lieber-DeCarli protocol) on hepatic vitamin A storage, expression of smooth muscle alpha-actin, and sinusoidal contractility in Sprague-Dawley rats. Using in vivo epifluorescence video microscopy, we quantified the number of sites of vitamin A fluorescence (purportedly stellate cells) and assessed sinusoidal microhemodynamics at baseline and during a 20-minute infusion period of ET-1 (1 pmol * 100 g body weight [bw]1min-1). Retinol and retinyl palmitate were measured after the experiment by means of high-pressure liquid chromatography (HPLC). A highly significant decrease in liver retinyl palmitate level (control: 622.5 +/- 50.9; ethanol: 273.0 +/- 38.0 microgram/g liver; P< .001) was found that correlated with a decrease in sites of vitamin A fluorescence (control: 531.4 +/- 76.1; ethanol: 141.1 +/- 30.2* mm-2; r = .82, P <.001). Concomitantly scattered expression of smooth muscle alpha-actin in sinusoids was observed. Although sinusoidal hemodynamics were not affected at baseline, a significant increase in sinusoidal contractility on endothelin-1 infusion (e.g., sinusoidal resistance [% of baseline value]: control: 10 minutes: 288.7 +/- 71.7, 20 minutes: 200.5 +/- 46.9; ethanol: 10 minutes: 1,916.0 +/- 701.7, 20 minutes: 656.8 +/- 103.3; P < .05 and .01, respectively) was observed. These data indicate that chronic ethanol consumption in this moderate model initiates stellate cell activation. Increased sinusoidal responsiveness to the vasoconstrictor ET-1 in vivo may contribute to the increased susceptibility of ethanol-fed rats to secondary stresses that increase ET-1 expression, such as endotoxemia.
最近的证据表明，肝星状细胞起着肝脏特异性周细胞的作用，对内皮素-1（ET-1）有高度收缩反应。肝损伤已被证明会导致星状细胞“激活”，使其表型转变为更具肌成纤维细胞特征的细胞类型，包括维生素A的丢失和收缩性增加。本研究旨在测试短期慢性乙醇摄入（根据Lieber-DeCarli方案，占总热量的36%，持续5周）对Sprague-Dawley大鼠肝脏维生素A储存、平滑肌α-肌动蛋白表达以及肝血窦收缩性的影响。使用体内落射荧光视频显微镜，我们在基线时以及在ET-1（1 pmol×100 g体重[bw]×1×min-1）输注20分钟期间，对维生素A荧光位点（据称是星状细胞）的数量进行了定量，并评估了肝血窦微血流动力学。实验结束后，通过高压液相色谱（HPLC）测量视黄醇和棕榈酸视黄酯。发现肝脏棕榈酸视黄酯水平显著降低（对照组：622.5±50.9；乙醇组：273.0±38.0微克/克肝脏；P<.001），这与维生素A荧光位点的减少相关（对照组：531.4±76.1；乙醇组：141.1±30.2个/mm-2；r=.82，P<.001）。同时，观察到肝血窦中平滑肌α-肌动蛋白的散在表达。虽然基线时肝血窦血流动力学未受影响，但在输注内皮素-1时肝血窦收缩性显著增加（例如，肝血窦阻力[相对于基线值的%]：对照组：10分钟：288.7±71.7，20分钟：200.5±46.9；乙醇组：10分钟：1916.0±701.7，20分钟：656.8±103.3；分别为P<.05和P<.01）。这些数据表明，在这个中度模型中，慢性乙醇摄入会引发星状细胞激活。体内肝血窦对血管收缩剂ET-1的反应性增加，可能导致乙醇喂养的大鼠对增加ET-1表达的继发性应激（如内毒素血症）的易感性增加。
