目的评价L-鸟氨酸-L-门冬氨酸(LOLA)治疗肝硬化肝性脑病(HE)的疗效和安全性。方法计算机检索MEDLINE、PubMed、EMBase、The Cochrane Central Register of Controlled Trials、中国生物医学文献数据库、中国科技期刊数据库(维普)、中国...目的评价L-鸟氨酸-L-门冬氨酸(LOLA)治疗肝硬化肝性脑病(HE)的疗效和安全性。方法计算机检索MEDLINE、PubMed、EMBase、The Cochrane Central Register of Controlled Trials、中国生物医学文献数据库、中国科技期刊数据库(维普)、中国期刊全文数据库和万方数字化期刊全文数据库。中文检索词为:L-鸟氨酸-L-门冬氨酸、肝硬化、肝性脑病、随机对照试验;英文检索词为:L-ornithine-L-aspartate,hepatic cirrhosis,hepaticencephalopathy,randomized controlled trial。检索LOLA治疗肝硬化HE的临床随机对照试验,采用Cochrane图书馆提供的Review Manager 3.4软件对纳入的研究进行Meta分析。结果共纳入6项研究,包括512例肝硬化HE患者。纳入研究的主要结局指标有:(1)疾病临床缓解率;(2)血氨值;(3)缩短数字连接试验A(NCT-A)反应时间;(4)药物不良反应发生情况。纳入研究的Jadad评分为3～5分,均为高质量临床随机对照研究。Meta分析结果显示:(1)LOLA组HE临床缓解率高于对照组〔RR=1.49,95%CI(1.10,2.01),P=0.010〕;亚组分析结果显示,LOLA组轻微肝性脑病(MHE)临床缓解率高于对照组〔RR=2.25,95%CI(1.33,3.82),P=0.003〕,显性肝性脑病(OHE)临床缓解率也高于对照组〔RR=1.31,95%CI(1.15,1.50),P<0.0001〕。(2)LOLA组血氨值下降程度大于对照组〔WMD=-10.22,95%CI(-13.70,-6.75),P<0.00001〕。(3)LOLA组NCT-A反应时间短于对照组〔WMD=-10.34,95%CI(-14.87,-5.80),P<0.00001〕。(4)LOLA组药物不良反应发生率(13.0%)低于对照组(10.6%)〔RR=1.22,95%CI(0.69,2.17),P=0.49〕。结论现有的临床研究证据表明,LOLA可提高肝硬化HE患者疾病临床缓解率,对MHE和OHE同样有效,可明显降低肝硬化HE患者血氨水平,缩短NCT-A反应时间,且不良反应发生率低、疗效肯定、安全性好。展开更多
目的系统评价L-鸟氨酸-L-门冬氨酸(L-ornithine-L-aspartate,LOLA)治疗肝性脑病(hepaticencephalopathy,HE)的疗效和不良反应。方法计算机检索PubMed、EMbase、Web of Science、e CochraneCentral Register of Controlled Trials(CENTR...目的系统评价L-鸟氨酸-L-门冬氨酸(L-ornithine-L-aspartate,LOLA)治疗肝性脑病(hepaticencephalopathy,HE)的疗效和不良反应。方法计算机检索PubMed、EMbase、Web of Science、e CochraneCentral Register of Controlled Trials(CENTRAL)、CNKI、VIP、WanFang Data(检索时间截至2011年11月30日),纳入LOLA治疗肝性脑病的随机对照试验(RCT),由两位评价员独立评价纳入研究的质量、进行资料提取和交叉核对后,采用RevMan 5.0软件进行Meta分析。结果纳入6个RCT,C型HE患者432例,A型HE患者185例。Meta分析结果显示:与安慰剂相比,LOLA能明显降低C型HE患者的血氨水平[WMD=16.60,95%CI(8.34,24.85,P<0.000 1],改善数字连接试验(NCT-A)反应时间[WMD=9.6,95%CI(5.26,13.93),P<0.000 1],有效提高HE临床缓解率[RR=1.36,95%CI(1.06,1.73),P=0.01];但LOLA对于A型HE的疗效与安慰剂相比,差异无统计学意义(P>0.05)。结论 LOLA对C型HE患者疗效肯定,在临床上可作为一种治疗选择;但对A型HE的疗效有待更多高质量RCT进一步评价。展开更多
Aim L-Arginine· L-aspartate, a double salt, has been recently reported toinhibit platelet aggregation and thrombosis, but its action mechanism is not clear yet. This studywas conducted to investigate its effect o...Aim L-Arginine· L-aspartate, a double salt, has been recently reported toinhibit platelet aggregation and thrombosis, but its action mechanism is not clear yet. This studywas conducted to investigate its effect on FITC-PAC-1, an anti-glycoprotein IIb/IIIa monoclonalantibody binding to activated platelets, and on correlative autacoid levels in plasma or inplatelets in order to explore its potential pathway of inhibiting platelet aggregation andthrombosis. Methods Monoclonal antibody binding to activated platelets was assayed by flowcytometry; NO was assessed by colorimetric method. cAMP, TXB_2 or 6-keto-PGF_(1α) levels wereassessed by radioimmunoassay. Results Gavaged 30 mg·kg^(-1) of L-arginine·L-aspartate increasedboth concentration of NO in plasma and 6-keto-PGF_(1) in incubated supernatant of aortic segment ofrats ex vivo (P < 0.05), but it did not influence cAMP content in platelets and the level of TXB_2or 6-keto-PGF_(1) in plasma of rats, whereas ASA significantly lowered TXB_2 or 6-keto-PGF_(1α) inplasma. Both 100 μmol-L^(-1) of L-arginine ·L-aspartate and ASA inhibited FITC-PAC-1 binding toactivated platelets in vitro. Conclusion The increase in NO and PGI_2 release from endo-thelialcells and consequent inhibition of platelet activation may contribute to the inhibition of plateletaggregation and thrombosis by L-arginine· L-aspartate; whereas arachidonic acid or cAMP metabolicpathway is not closely correlative with the studied effect.展开更多
文摘Aim L-Arginine· L-aspartate, a double salt, has been recently reported toinhibit platelet aggregation and thrombosis, but its action mechanism is not clear yet. This studywas conducted to investigate its effect on FITC-PAC-1, an anti-glycoprotein IIb/IIIa monoclonalantibody binding to activated platelets, and on correlative autacoid levels in plasma or inplatelets in order to explore its potential pathway of inhibiting platelet aggregation andthrombosis. Methods Monoclonal antibody binding to activated platelets was assayed by flowcytometry; NO was assessed by colorimetric method. cAMP, TXB_2 or 6-keto-PGF_(1α) levels wereassessed by radioimmunoassay. Results Gavaged 30 mg·kg^(-1) of L-arginine·L-aspartate increasedboth concentration of NO in plasma and 6-keto-PGF_(1) in incubated supernatant of aortic segment ofrats ex vivo (P < 0.05), but it did not influence cAMP content in platelets and the level of TXB_2or 6-keto-PGF_(1) in plasma of rats, whereas ASA significantly lowered TXB_2 or 6-keto-PGF_(1α) inplasma. Both 100 μmol-L^(-1) of L-arginine ·L-aspartate and ASA inhibited FITC-PAC-1 binding toactivated platelets in vitro. Conclusion The increase in NO and PGI_2 release from endo-thelialcells and consequent inhibition of platelet activation may contribute to the inhibition of plateletaggregation and thrombosis by L-arginine· L-aspartate; whereas arachidonic acid or cAMP metabolicpathway is not closely correlative with the studied effect.
