摘要
目的评估外源性牛磺酸对胆红素脑病(bilirubinencephalopathy,BE)乳鼠模型脑顶叶皮质水通道蛋白4(aquaporin4,AQP4)表达的调控作用,明确其对BE的治疗效果及潜在分子机制。方法选取体质量10~15g的新生SD乳鼠,随机分为假手术组(Sham组)、胆红素脑病组(BE组)及牛磺酸治疗组(BE+Tau组)。其中,BE组腹腔注射牛磺酸溶剂,4h后经小脑延髓池注射胆红素(20mg/kg)诱导BE模型;BE+Tau组先腹腔注射牛磺酸(15mg/kg),4h后经小脑延髓池注射胆红素;Sham组先腹腔注射牛磺酸溶剂,4h后经小脑延髓池注射胆红素溶剂。造模后观察各组乳鼠神经行为学表现。各组于造模24h后取脑,采用苏木精-伊红染色及尼氏染色评估神经细胞损伤程度;通过干湿重法测定脑含水量;利用罗丹明B异硫氰酸酯渗漏法明确BE脑水肿类型;采用Westernblot检测脑顶叶皮质AQP4表达水平。结果与Sham组相比,BE组乳鼠出现角弓反张、爬行不稳等明显神经行为学异常,脑含水量显著高,神经细胞水肿损伤明显,脑水肿类型为细胞毒性水肿,且脑顶叶皮质AQP4表达显著上调;与BE组相比,BE+Tau组乳鼠神经行为学异常明显减轻,脑含水量低,神经细胞水肿损伤改善,未结合胆红素诱导的AQP4表达上调被显著抑制。结论外源性牛磺酸可通过抑制未结合胆红素所致BE乳鼠脑顶叶皮质AQP4表达上调,延缓细胞毒性水肿发生,减轻神经细胞损伤,从而抑制BE进展。
Objective To evaluate the regulatory effect of exogenous taurine(Tau)on the expression of aquaporin 4(AQP4)in the parietal cerebral cortex of a rat pup model of bilirubin encephalopathy(BE)and clarify its therapeutic effect on BE and the underlying molecular mechanism.Methods Neonatal SD rats weighing 10-15 g were randomly divided into three groups:sham operation group(Sham group),bilirubin encephalopathy group(BE group),and taurine treatment group(BE+Tau group).The BE group was intraperitoneally injected with taurine solvent,followed by cisterna magna injection of bilirubin(20 mg/kg body weight)4 hours later to induce the BE model.The BE+Tau group was first intraperitoneally injected with taurine(15 mg/kg body weight),and bilirubin was injected via cisterna magna 4 hours later.The Sham group was first administered with taurine solvent via intraperitoneal injection,followed by an injection of bilirubin solvent via cisterna magna at 4 hours post the initial treatment.After modeling,the neurobehavioral manifestations of rats in each group were observed.At 24 hours after modeling,brain tissues were harvested from all rat pups.HE staining and Nissl staining were used to assess the degree of neuronal damage.The water content of brain tissue was measured by the dry-wet weight method.Rhodamine B isothiocyanate leakage assay was used to determine the type of cerebral edema in BE.Western blot was employed to detect the expression level of AQP4 in the parietal cortex.Results Compared with the Sham group,rats in the BE group showed obvious neurobehavioral abnormalities such as opisthotonus and unsteady crawling,significantly increased brain water content,obvious neuronal edema and damage,and the type of cerebral edema was cytotoxic edema.Additionally,the expression of AQP4 in the parietal cortex was significantly upregulated.Compared with the BE group,the neurobehavioral abnormalities of rats in the BE+Tau group were significantly alleviated,the brain water content was decreased,the neuronal edema and damage were improved,and the upregulation of AQP4 expression induced by unconjugated bilirubin(UCB)was significantly inhibited.Conclusion Exogenous taurine can delay the occurrence of cytotoxic edema,alleviate neuronal damage,and thereby inhibit the progression of BE by suppressing the UCB-induced upregulation of AQP4 expression in the parietal cortex of BE neonatal rats.
作者
樊萍
高宇阳
肖泽宇
董泽琳
郭可云
毛玢懿
陈屿潇
张妤涵
甘胜伟
FAN Ping;GAO Yuyang;XIAO Zeyu;DONG Zelin;GUO Keyun;MAO Binyi;CHEN Yuxiao;ZHANG Yuhan;GAN Shengwei(Department of obstetrics and Gynecology,Chongqing University Affiliated Renji Hospital(the Fifth People's Hospital of Chongqing),Chongqing 401336,China;University of Leicester Joint Institute,Chongqing Medical University,Chongqing 400016,China;National Demonstration Center for Experimental Basic Medical Education Teaching,Chongqing Medical University,Chongqing 400016,China;Department of Human Anatomy,School of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,China)
出处
《医学研究与教育》
2026年第1期1-10,共10页
Medical Research and Education
基金
重庆市大学生创新创业训练计划项目(S202510631085)
重庆医科大学第二临床学院第六届“启航宽仁”大学生创新创业训练自主项目(2)。
