摘要
目的：观察急性肝衰竭动物模型应用抗内毒素中药制剂复方茵陈方抗内毒素血症治疗的疗效。观察抗内毒素血症疗法联合西医治疗慢性乙型重型肝炎临床疗效。
方法：将实验大白鼠分成4组(正常对照组、中毒组、治疗组、预防加治疗组),以D-氨基半乳糖制备急性肝衰竭模型,并对治疗组及预防加治疗组以抗内毒素中药制剂复方茵陈方治疗,动态观察4组实验大白鼠血浆内毒素(ET)水平的变化、血浆内毒素(ET)与血浆过氧化脂质(LPO)、血浆纤维结合素(Fn)水平的关系及肝脏病理变化。以天津市传染病医院重型肝炎科2009年6月至2009年12月收治的慢性乙型重型肝炎患者63例作为研究对象,按照2：1比例随机分为治疗组42例,对照组21例,对照组采用西医基础治疗和对症支持治疗,治疗组在对照组治疗基础上联合口服复方茵陈方及中药保留灌肠治疗,疗程8周。观察两组患者治疗8周时总病死率、生存曲线,治疗2周时临床症状改善情况,治疗前、治疗2周、4周、6周及8周时凝血酶原时间的国际标准化比值(INR)、总胆红素(TBiL)、白蛋白(ALB)、胆碱酯酶(CHE)以及终末期肝病模型(MELD)评分变化,治疗前和治疗4周时ET、肿瘤坏死因子-α(TNF-α)、LPO水平变化,以及治疗期间治疗组不良反应发生情况。
结果：注射D-氨基半乳糖24小时后均有内毒素血症的发生,与正常对照组对比差异有统计学意义(P<0.01)。中毒组大鼠在24、36、48小时血浆ET水平呈逐渐升高趋势,60小时达高峰,72小时有下降趋势。治疗组与对中毒组比较各时相ET水平均低于中毒组。预防加治疗组与治疗组比较,各时相均低于治疗组ET水平。治疗组LPO低于中毒组,预防加治疗组LPO各时相均低于中毒组,24、36、60小时均低于治疗组。实验各组在中毒后24小时Fn水平均略有下降,与正常对照组比较,经统计学处理差异有统计学意义(P<0.01),72小时中毒组Fn与治疗组及预防加治疗组比较差异均有统计学意义(均P<0.01)。肝脏病理变化预防加治疗组损伤最轻,治疗组次之,中毒组最重。两组患者8周治疗期间共死亡20例,其中治疗组11例,对照组9例。治疗组总病死率26.2%,对照组总病死率42.9%。治疗组在治疗期间存活率均高于对照组。治疗2周时,两组患者乏力、腹胀、食欲不振均较治疗前改善,治疗组患者的乏力、食欲不振改善与对照组比较差异均有统计学意义(均P<0.05)。两组患者治疗前INR值、TBiL、ALB、CHE、MELD评分、ET、TNF-α、LPO基线水平一致,差异均无统计学意义(均P>0.05)。随着治疗周数增加,两组患者INR值、TBiL水平及MELD评分逐步下降,ALB、CHE水平有所升高,从治疗2周时起治疗组TBiL水平与对照组比较差异有统计学意义(均P<0.05),从治疗4周时起治疗组患者的INR值、MELD评分与对照组比较差异均有统计学意义(均P<0.05)。治疗8周时治疗组患者的ALB水平与对照组比较差异有统计学意义(P<0.05)。治疗2周、4周、6周及8周时治疗组与对照组患者的CHE水平比较差异均无统计学意义(均P>0.05)。治疗前2组患者全部发生内毒素血症,ET含量均在160pg/ml以上。治疗4周时,治疗组患者的ET、TNF-α和LPO水平均较治疗前下降且均低于对照组。治疗组的ET、TNF-α和LPO水平与对照组比较差异有统计学意义(均p<0.05)。治疗组在治疗期间未发生与应用复方茵陈方及含大黄煎剂中药保留灌肠治疗相关不良反应。
结论：应用抗内毒素中药制剂复方茵陈方治疗可以明显降低急性肝衰竭动物血中ET、LPO水平,提升血浆Fn水平,减轻实验动物的肝损伤程度,表明复方茵陈方具有明显的抗内毒素、抗脂质氧化和保护肝细胞作用。在给予D-氨基半乳糖造模前加用抗内毒素中药制剂复方茵陈方预防,可以使治疗内毒素血症疗效更佳。抗内毒素血症疗法联合西医治疗慢性乙型重型肝炎患者,较单纯西医治疗可以更有效降低病死率、改善患者临床症状,更有效降低ET、TNF-α、LPO、TBiL、INR值以及MELD评分,提高ALB水平,具有抗内毒素、抗脂质氧化、减轻肝脏炎症坏死,提高肝脏合成储备能力,改善凝血功能障碍等作用,是临床治疗慢性乙型重型肝炎的一个有效可行方案。
Aims:To observe the efficacy of anti-endotoxin traditional Chinese medicine, compound oriental wormwood decoction, on the animal model of acute liver failure. To observe the therapeutic effect of treating chronic severe hepatitis B cases by the integration of anti-endotoxemia of traditional Chinese and western medicine.
Methods:The experimental rats were divided into four groups (normal control group, the poisoning group, treatment group, prevention plus treatment group) prepared acute liver failure animal model by D-galactosamine. Thereafter, the treatment group and the prevention plus treatment group were treated with anti-endotoxin traditional Chinese medicine known as compound oriental wormwood decoction. Plasma endotoxin (ET), plasma lipid peroxide (LPO), plasma fibronectin (Fn) levels and liver pathology changes of four groups are constantly observed. The study selected 63 cases of chronic severe hepatitis B which were hospitalized in the wards of serious hepatitis in Tianjin infectious disease hospital from September 2009 to December 2009.They were randomly devided into 2 groups by the ratio of 2:1, with 21 cases in the control group following the basic western medicine and supportive therapy and the resting 42 cases in the treatment group receiving compound oriental wormwood decoction and retention-enema of Chinese medicine based on the basic western medicine and supportive therapy.Both groups of patients were observed for 8 weeks, during which Several key factors such as the total fatality rate,survival curve,,the improvement of clinical symptom after 2 weeks of both groups were closely observed. In addition,we study the level of blood INR,TBiL,ALB,CHE and MELD score before treatment and 2 weeks,4 weeks,6 weeks and 8 weeks after treatment.The level of ET, TNF-a and LPO before treatment and after 4 weeks treatment and the side effects of the treatment group were also be recorded.
Results:Statistically significant difference (P<0.01) was noted after the injection of galactosamine within 24 hours, since the endotoxemia occurred when compared with the normal group. The plasma ET level of Poisoning rats gradually increased after 24,36 or 48 hours, reaching a peak after 60 hours and then dropping after 72 hours. The all time ET level in treatment group was lower than poisoning group. What's more, the LPO of treatment group was lower than that of the poisoning group and the LPO of prevention plus treatment group were also lower than the poisoning group and than that of the treatment group in the hour 24,36,60.24 hours after the poisoning, the Fn levels of all experimental groups were slightly decreased compared with the control group with statistically significant difference (P<0.01), statistically significant difference (P<0.01) was also found between poisoning prevention group and treatment group or untreated group after 72 hours. In terms of the liver pathological changes, the prevention of the treatment group is the minimum and the treatment group followed while the poisoning group is most serious.20 cases died during 8 weeks, of which 11 patients were in the treatment group and 9 in the control group,with the total morbidity 26.2% in the treatment group and 42.9% in the control group respectively. Therefore, the survival rate was higher in the treatment group than that of the control group during the period of treatment.After 2 weeks treatment, the symptoms like fatigue,abdominal distension,inappetency were much improved in both groups. Compared with the control groups,the index of the treatment group had significant difference in the improvement of fatigue, inappetency and yellowish and greasy tongue fur (all P<0.05).There was no significant difference in the level of INR,TBiL,MELD score,ET,TNF-αand LPO between two groups before treatment(all P>0.05). Gradual decline in the blood level of INR、TBiL and MELD score was noted while a upward trend in the blood level of ALB,CHEfor was detected during the successive 8 weeks.Compared with the control groups,the treatment group had significant difference in TBiL after 2 weeks treatment, in INR and MELD score since 4 weeks treatment and in ALB after 8 weeks treatment (all P<0.05).There was no significant difference in the level of CHE between two groups (all P>0.05).Both of the two groups suffered from ETM before treatment. The level of ET of the two groups was all above 160pg/ml. After 4 weeks, patients treated with ET, TNF-αand LPO were lower than those before treatment and even lower than those of the control group with statistically significant difference (all P<0.05). adverse effects were not detected in any group during treatment.
Conclusions:The application of compound oriental wormwood decoction of anti-endotoxin traditional Chinese medicine can significantly reduce the acute liver failure of endotoxin in animal blood, plasma lipid peroxide levels, elevating plasma fibronectin level, reducing the extent of liver injury of experimental animals, which indicated that the compound oriental wormwood decoction has obvious effects on anti-endotoxin, anti-lipid peroxidation and protection of liver cells. As it showed, Before giving D-galactosamine to make the animal model, the application of compound oriental wormwood decoction of anti-endotoxin traditional Chinese medicine can make better effect as a prevention.The integration of anti-endotoxemia of traditional Chinese medicine and western medicine can better decrease the fatality rate,improving the clinical symptom and the level of ALB while decreasing the level of ET,TNF-a,,LPO,TBiL,INR and MELD score. It has the functions of anti-endotoxin, anti-lipoid oxidation,relief of the inflammation and necrosis of liver. It may better increase the synthesis and storage capability of the liver,improve the coagulation disorders than the western medicine and supportive therapy,, providing a better way to treat chronic severe hepatitis B.
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