Calycosin alleviates hyperbilirubin nerve injury in Ugt1-/- mice by inhibiting oxidative stress,apoptosis, and mitochondrial function

Background and purposeHyperbilirubinemia is a common condition in neonates that is associated with poor neurodevelopmental outcomes. Although studies have proposed that calycosin has a neuroprotective effect, the exact molecular mechanism underlying calycosin treatment of hyperbilirubinemia remains elusive. To fill this gap, we analyzed the mechanism of calycosin treatment in hyperbilirubinemia model mice.MethodThirty neonatal mice were randomly divided into wide type (WT), Ugt1^-/- and calycosin treatment group. Neuronal damage was observed with Nissl staining. Immunofluorescence staining were carried out to determine DNA damage repair and neurodegeneration. Oxidative stress was investigated by immunostaining with 4-hydroxynonenal (4-HNE). Western blot (WB) and Qpcr were used to detect relative protein and mRNA expression levels. Mitochondrial CI/CII activity of mitochondria was analyzed with a spectrophotometer.ResultThe total bilirubin concentration was significantly higher in Ugt1-/- group compared with WT, but calycosin treatment reduced concentration of bilirubin. The total bilirubin and bilirubin/albumin ratio were significantly higher at postnatal day 4 compared with day 2. Calycosin treatment reduced serum bilirubin concentration and bilirubin/albumin ratio. After calycosin treatment, Nissl body count increased, apoptosis-related protein was downregulated and 4-HNE level decreased.Compared with Ugt-/- group, calycosin treatment increased neurons (NeuN+) and calbindin positive cells and decreased fluorojade C(FJC)positive neurons in WT group. In mitochondria, calycosin alleviated mitochondrial electron transport chain dysfunction in Ugt1-/- mice.ConclusionWe demonstrated that the mechanism of calycosin treatment on hyperbilirubinemia-induced Ugt1^-/- was associated mainly with antioxidant effects, antiapoptosis and inhibition of normal mitochondrial function.     

新生儿高胆红素血症181例病因分析

目的:了解本地新生儿高胆红素发生的主要病因,为临床治疗新生儿高胆红素血症及预后判断提供参考依据.方法:对181例新生儿高胆红素血症患儿的病因进行统计分析.结果:围生因素66例(36.5%),感染52例(28.7%),母乳性黄疽38例(21%),溶血因素23例(12.7%),其他病因2例(1.1%).结论:加强围生期保健,防止各种高危因素的发生,加强抗感染,正确母乳喂养并及时处理新生儿期的并发疾病,是降低新生儿高胆红素血症的关键.     

大剂量腺苷蛋氨酸治疗严重慢性肝病所致高胆红素血症的疗效观察

目的观察大剂量腺苷蛋氨酸对各种原因导致的高胆红素血症的疗效。方法严重慢性肝病患者63例(病毒性肝炎所致肝硬化39例,酒精性肝硬化18例,药物性肝病2例,原发性胆汁性肝硬化4例)。入院时平均血清胆红素水平为195.1 mmol/L,经常规保肝治疗4周后,肝功能无明显改善,胆红素水平升高。在原治疗基础上,加大腺苷蛋氨酸剂量至2.0 g,2次/d静推。每周复查肝功能,以血清总胆红素水平作为主要观察指标。结果 63例患者中,3例乙肝和酒精混合因素的肝硬化在入组治疗不足2周时,因出现消化道大出血而退出观察。60例患者治疗满4周,胆红素水平明显下降,与常规保守治疗后胆红素水平相比,差异有统计学意义(P<0.01)。结论在某些严重肝病所导致的严重高胆红素血症患者,常规保肝治疗效果不佳时,可以尝试大剂量S-腺苷蛋氨酸治疗。     

丁二磺酸腺苷蛋氨酸治疗慢性乙型肝炎伴高胆红素血症的效果观察

目的观察丁二磺酸腺苷蛋氨酸治疗慢性乙型肝炎伴高胆红素血症者的疗效。方法将我院2009年12月～2011年12月收治的60例慢性乙型肝炎伴高胆红素血症患者随机分为两组,两组分别采用丁二磺酸腺苷蛋氨酸、苦黄治疗。4周后进行疗效观察。结果丁二磺酸腺苷蛋氨酸组总有效29例（96．7％）,苦黄组总有效20例（66．7％）,两组间治疗效果差异具有统计学意义（P=0）。结论丁二磺酸腺苷蛋氨酸疗效优于苦黄。     

新生儿高胆红素血症神经毒性作用的监测

目的探讨高胆红素血症神经毒性对新生儿神经行为的影响。方法回顾性分析我院2008年1月。2011年10月收治入院的足月新生儿高胆红素血症患儿160例（观察组）临床资料,另选择我院同期正常足月生理性黄疸新生儿160例作为对照组,两组均采用总胆红素与白蛋白比值（B／A）与脑干听觉诱发电位（ABR）进行检测．并测查新生儿神经行为（NBNA）进行比对。结果观察组TBC、B／A比值测定结果与对照组比较差异有统计学意义（均P〈0．05）。ABR111波、V波潜伏期及I-Ⅲ、I-V波间期与对照组相比,差异均有统计学意义（均P〈0．05）。①高胆患儿NBNA评分均低于对照组,两者差异均有统计学意义。观察组NBNA评分均低于对照组,两者差异均有统计学意义（均P〈0．05）@B／A与NBNA评分的直线相关分析显示两者之间具有负相关关系（r=-0．46,P〈0．05）。结论①NBNA评分可应用早期诊断高胆所致的脑损伤。②B／A可作为评估胆红素神经毒性危险因素的指标之一。@ABR对了解新生儿早期听神经及脑干功能障碍有重要价值。     

高胆红素血症新生儿血清神经元特异性烯醇化酶水平变化及意义

目的探讨血清神经元特异性烯醇化酶（s—NSE）水平与新生儿行为神经测定（NBNA）的相关性,探讨s—NSE在急性胆红素脑病（ABE）发生、发展中的价值。方法对63例高胆红素血症新生儿在高胆期及黄疸消退后分别采用电化学发光免疫法测定s—NSE及行NBNA,生后1、3、6个月追踪随访,并与24例正常新生儿对照。结果高胆期：s-NSE水平随血清总胆红素（TSB）升高而升高,各组s—NSE水平比较差异有统计学意义（F=56．287,P〈0．01）;高胆组NBNA评分明显下降,NBNA评分随TSB升高而降低,各组NBNA评分比较差异有统计学意义（F=50．247,P〈0．01）;s—NSE水平与NBNA评分间呈显著负相关（r=-0．609,P〈0．01）。高胆消退后,s—NSE水平均有明显下降,NBNA评分同步上升。结论高胆红素血症患儿s—NSE浓度显著升高,与NBNA评分呈负相关,可以作为临床早期监测新生儿是否进入ABE的危险期的一个生物学指标。     

换血治疗新生儿高胆红素血症的预后分析

目的评价换血疗法对新生儿高胆红素血症的预后,以积累临床经验,指导临床工作。方法跟踪观察43例应用外周动静脉同步换血治疗的高胆红素血症的新生儿作为观察组,观察治疗后10～12个月时听力、发育及神经运动功能的状况。选取同期未应用换血治疗的高胆红素血症新生儿43例作为对照组。结果观察组患儿在听力、发育及神经运动功能方面明显优于对照组。结论换血治疗新生儿高胆红素血症,在改善患儿听力、发育及神经运动功能方面有重要价值,可以临床中推荐应用。     

早期综合干预预防新生儿高胆红素血症疗效观察

目的观察综合干预措施（早期诱导排便、日光浴、口服菌栀黄口服液）对新生儿高胆红素血症的预防作用。方法将我院2006年1月至2007年2月产科出生的足月正常新生儿960例随机分为综合干预组和非综合干预组。根据惠儿情况,分阶段进行早期诱导排便、日光浴、口服菌栀黄口服液等措施,然后前瞻性的观察患儿高胆红素血症的发生情况。结果早期综合千预组高胆红素血症的发生率明显低于非综合干预组,两组之间比较差异有统计学意义（P〈0．01）,综合干预组较非综合干预组高胆红素血症的发生时间晚（P〈0．01）、持续时间短（P〈0．01）。结论早期诱导排便、日光浴、口服菌栀黄口服液等综合干预措施能减少新生儿高胆红素血症的发生率和持续时间。     

Association of bilirubin and protein thiols in relation to copper and ceruloplasmin in hyperbilirubinemic patients

Objective： Bilirubin is a double edged sword in biological system, acting as a toxic molecule and cytoprotectant. Unconjugated bilirubin is proved to show antioxidant activity in vitro and in vivo. In the current work we tried to know the relationship between both conjugated and uneonjugated bilirubin with copper and protein thiols in patients with hyperbilirubihernia. Methods： Study was conducted on 56 hyperbilirubinemie eases and 56 healthy controls. Serum copper, ceruloplasmin, protein thiols, total bilirubin, conjugated and unconjugated bilirubin, uneonjugated bilirubin/albumin ratio, total protein, albumin, AST, ALT and ALP were estimated. Results： There was significant increase in serum copper, total biliruhin, conjugated and uneonjugated bilirubin, uneonjugated bilirubin/albumin ratio, AST, ALT, and ALP, and decrease in serum ceruloplasmin, protein thiols, total protein, and albumin in hyperbilirubinemie cases when compared to healthy controls. Conjugated bilirubin correlated positively with liver enzymes AST and ALP, and negatively with protein thiols, total protein and albumin. Uneonjugated bilirubin correlated positively with ALT. Protein thiols correlated negatively with copper and positively with eeruloplasmin, and also correlated negatively with liver enzymes like AST, ALT and ALP, and positively with total protein and albumin. Conclusion： Combination of elevated levels of trace elements like copper and availability of reducing agent like bilirubin may prove deleterious by generating free radicals.     

高胆红素血症新生儿63例肾功能状况的追踪观察

目的追踪观察高胆红素血症新生儿肾功能损害的变化规律,探讨高胆红素血症新生儿肾功能损害的预后和转归。方法对63例高胆红素血症（高胆组）和30例非高胆红素血症（非高胆组）的新生儿出生后第3天进行血尿素氮、肌酐和血β2-微球蛋白测定,并对高胆组新生儿出生后第7、10、14、21天进行血B：．微球蛋白测定。结果出生后第3天高胆组血β2-微球蛋白（4．43±0．8）mg·L^-1高于非高胆组（1．50±0．26）mg·L^-1,差异有统计学意义（P〈0．01）;且中度高胆组（4．54±0．22）mg·L^-1。高于轻度高胆组（3．49±0．29）mg·L^-1,差异有统计学意义（P〈0．05）;重度高胆组（5．34±0．16）mg·L^-1。高于中度高胆组,差异有统计学意义（P〈0．05）。轻、中、重度高胆组血β2-微球蛋白浓度分别在出生后第10、14、21天降至正常范围。高胆组血胆红素水平与血β2-微球蛋白浓度经线性相关分析呈高度直线正相关（r=0．96,P〈0．01）。结论新生儿高胆红素血症时血β2-微球蛋白明显增高,存在肾小球滤过率的下降,并随着血胆红素浓度的增加而加剧,高胆程度越重其恢复越慢,但高胆所至的肾功能损害是暂时性的,预后良好。