肝癌自发性破裂与血管病变

SPONTANEOUR RUPTURE OF HEPATOCELLULAR CARCINOMA AND VASCULAR INJURY

目的 探讨肝癌自发性破裂的发病机理。方法 选用肝癌破裂及非破裂的患者标本各 39例 ,采用免疫组化法检测其与血管病变有关的因素包括 :第八因子相关抗原 (v WF因子 ) ,弹性硬蛋白 ,弹性蛋白酶 (中性粒细胞性 ) ,IV型胶原蛋白和胶原蛋白酶。结果 与非破裂组相比 ,肝癌破裂患者中的血管内皮 v WF因子表达量明显下降 (v WF因子染色阳性的血管面积 :15 8μm2 vs36 3μm2 ,P<0 .0 0 1)。血管壁中弹性蛋白酶分布异常、弹性硬蛋白增生过度 (血管壁弹性硬蛋白厚度 :2 0 μm vs9μm,P<0 .0 1)、弹力膜断裂、胶原蛋白酶分泌量增加 (血管壁胶原酶染色阳性率 :95 % vs 5 0 % ,P<0 .0 0 1)及胶原蛋白被分解 (血管壁 IV胶原蛋白层厚度 :5μm vs 14μm,P<0 .0 0 1)。v WF因子为血管受损指标之一 ,并参与凝血过程。低表达量的 v WF因子说明肝癌破裂患者的血管有病变情况存在 ,并伴随凝血功能下降。血管损发生后 ,随即释放的细胞因子将刺激血管壁细胞合成过量弹性硬蛋白及胶原蛋白酶 ,导致弹性硬蛋白增生过度、血管弹性消失。由于胶原蛋白是血管壁张力的主要支撑结构 ,血管受损后 ,受刺激释放放的胶原蛋白酶可分解胶原蛋白层 ,使其血管壁支撑力下降。同时中性粒细胞亦可浸润受损的血管壁并释放弹性蛋白酶 。

Objective The purpose of this study is to define the mechanism related to spontaneous rupture of hepatocellular carcinoma(HCC).Methods Is this study ,we examined semiquantitatively the expression of angiogenesis factors including von Willebrand factor,elastin,neutrophil elastase,type IV collagen and collagenase in 30 specimens of HCC with spontaneous rupture by immunohistochemistry,and compared them with 30 specimens of HCC without rupture.Results Our results showed that there was a significant decrease of von Willebrand factor(158μm 2 vs 363μm 2,P<0.001),proliferation of degenerated elastin(20μm vs 9μm,P<0.01),abnormal distribution of neutrophil elastase,degradation of collagen IV(5μm vs 14μm,P<0.001) and increase in collagenase production(95% vs 50%,P<0.001) around the blood vessels in ruptured HCC.Since the decreased expression of von Willebrand factor is an indicator of vascular injury,and elastase and collagenase are present in inflammatory processes,we postulate that the vascular injury probably exists before spontaneous rupture of HCC occurs,and the blood vessel dysfunction resulting from the degeneration of elastin and the decrease of collagen IV render the blood vessels stiff and weak.The blood vessels split easily when the vascular load inereases from hypertension or minor mechanical trauma.Conclusion We conclude that spontaneous rupture of HCC may be related to the vascular dysfunction.