酒精对大鼠残肝再生的影响及丹参的保护作用

Effect of Chronic Ethanol Administration on Hepatic Regeneration in Rats and the Protection of Radix Salvia Mitiorrhiae

观察酒精对大鼠部分肝切除后残肝再生的影响以及中药丹参对酒精性肝病大鼠残肝再生的效果，以期初步探讨酒精性肝病的发生机制，同时为丹参在酒精性肝病防治方面的应用提供理论依据。方法：实验分３组①对照组１０只：每日自由饮食；②酒精组１０只：每天定量灌胃酒精外，鼠自由饮食；③丹参组１０只：在灌胃酒精（方法同酒精组）４周后，同时每日腹腔注射丹参注射液，１２０ｇ／ｋｇ／ｄ。各组大鼠至６周末行部分肝叶切除术，术后２４小时将大鼠处死，留取肝组织制备肝细胞悬液，行流式细胞术分析，绘制出ＤＮＡ直方图以增殖指数（ＰＩ）和Ｓ期比例（ＳＰＦ）表示细胞增殖活性。另取肝组织以１０％福尔马林固定，ＨＥ染色。结果：①肝细胞增殖周期时相分布情况：酒精组ＤＮＡ直方力冯Ｇ０／Ｇ１期细胞为主峰，但其峰值与对照组相比明显增加，Ｓ期峰抬高不明显，Ｇ２Ｍ峰较低平。丹参组ＤＮＡ直方图Ｇ０／Ｇ１峰明显低于酒精组，Ｓ期抬高及Ｇ２Ｍ峰较酒精组明显；②ＰＩ和ＳＰＦ对比：酒精组ＰＩ和ＳＰＦ值明显低于对照组及丹参组（Ｐ＜００５及＜００１），丹参组ＰＩ及ＳＰＦ值虽低于对照组，但两组比较差异无显著性（Ｐ＞００５）；③病理学：酒精组大鼠肝细胞明显肿胀，胞浆内可见大量脂滴?

Objective: To investigate effects of chronic ethanol administration on hepatic regeneration and the protection of Radix Salvia Mitiorrhiae(RSM) on these effects of ethanol.Methods: 30 rats were divided into three groups:①pair-fed:10 rats were offered by standard rat-chow and water ad libitium;②ethanol-fed:10 rats were received the same diet as pair-fed rats except that ethanol was intragastrically administrated at 8-12g/kg. W/d for 6 weeks; ③ RSM-used group:4 weeks following the ethanol administration as the ethanol group,RSM was used intraperitoneally at 12g/kg/d for 2 weeks simultaneously.All rats were performed a 70% hepatectomy and killed 24 hour later.Liver specimens were rapidly harvested for determination of liver regeneration and histological examination by Flow Cytometery(FCM) and light microscopy,respectively.Results:①The distribution of liver cell cycle:Percentage of G0/G1 phase was higher in ethanol group than in pair and RSM group.Peaks of S and G2M phases occurred obviously in pair and RSM groups;②Proliferative index(PI) and S phase fraction (SPF):The levels of PI and SPF stand for the proliferative capatcity of hepatocytes.PI and SPF were significantly lower in ethanol group than in pair and RSM groups ( P <0 05 and <0 01,respectively).There was no significant difference of PI and SPF between the pair and RSM group;③Pathology:Hepatocellular swelling and lipid droplet accumulation were more obvious in ethanol group than in pair and RSM groups.The karyokinesis of hepatocytes were hardly seen in ethanol group.Discussion: The results suggest that chronic ethanol administration can inhibit hepatocellular DNA synthesis and proliferative capacity.RSM can prevent heatocytes from alcoholic liver injury,increase liver regeneration capacity and reverse the inhibition of ethanol on liver regeneration.As the capacity of a patient to recover from a liver disease depends on the capacity of this liver to regenerate,impairment of liver cell renewal by ethanol could be a factor of major significance in the pathogenesis of alcoholic liver disease(ALD).RSM can play a protective role on ALD in some extend.