四氯化碳诱导犬早期肝损害所致门静脉高压的形态学观察

目的　探讨实验性犬肝脏早期损害所致的门静脉高压形成的形态学基础。方法　以小剂量四氯化碳 (CCl4)腹腔内注射诱导犬早期肝损害 ,制备门静脉高压犬模型。通过光镜、电镜观察肝脏形态学的改变。结果　腹腔内注射CCl47周后 ,共有 15头犬形成门静脉高压 (门静脉压力 2 2 7cmH2 O± 1 5cmH2 O ,1cmH2 O =0 0 98kPa,与给药前相比 ,P <0 0 5 )。HE染色示肝脏损害轻微。Masson染色、电镜 ,示肝窦毛细血管化。α 平滑肌肌动蛋白 (α SMA)免疫组化染色示肝星形细胞(HSC)大量活化。结论　肝脏受损早期 ,门静脉高压形成的可能原因是肝窦毛细血管化和HSC活化所致的肝窦血流阻力增加。

Morphology of portal hypertension at the early stage of liver damage induced by CCl4: an experimental study with dogs

OBJECTIVE: To explore the morphological basis of portal hypertension happened at the early stage of liver damage. METHODS: Sixteen mongrel dogs were injected intraperitoneally with carbon tetrachloride (CCl(4)) once a week for 4 weeks and then once every 4 days, totally for 7 weeks. Before the experiment and 7 weeks after the beginning of experiment, small pieces of liver tissues were taken through a median upper abdominal incision and underwent HE staining, Masson's staining, and immunohistochemistry with alpha-smooth muscle actin (alpha-SMA) to label the activated astrocyte (hepatic stellate cell, HSC), and transmission electron microscopy. The portal vein pressure was measured by puncture of gastroepiploic vein. The diameter of spleen was measure too. RESULTS: Since the second weeks after the experiment, the dogs showed vomiting, diarrhea, anorexia, weight loss, and varicose vein in the abdominal wall. One dog died of toxic enteritis 3 weeks after the beginning of experiment. 7 weeks after the injection of CCl(4), the average portal vein pressure of the rest 115 dogs was 22.7 cm H(2)O +/- 1.5 cm H(2)O, significantly higher than that before the experiment (12.2 cm H(2)O +/- 1.9 cm H(2)O, 1cm H(2)O = 0.098 kPa, P < 0.05). The long diameter of spleen of the 15 dogs was 24.4 +/- 3.1 cm, significantly greater than that before the experiment (18.7 cm +/- 2.4 cm, P < 0.05). Seven weeks after the injection of CCl(4) the appearance of liver did not change remarkably among the dogs, however, the spleens of the dogs showed swelling and stagnation of blood. No obvious ascites was seen. HE staining showed slight liver damage, such as fatty degeneration of liver cells; Masson's staining and electron microscopy showed typical sinusoid capillarization. alpha-SMA immunohistochemistry stain showed increased number of activated HSCs. Immunohistochemistry showed a number of alpha-SMA positive cells in the hepatic lobules. Portal hypertension was successfully induced in 15 dogs. CONCLUSION: At the early stage of liver damage the possible cause of portal hypertension is the increased resistance of blood stream due to sinusoid capillarization and activation of HSC.