新生猕猴溶血性高胆红素血症模型的建立

Hyperbilirubinemia models caused by hemolysis in newborn rhesus monkeys

目的建立新生猕猴溶血性高胆红素血症动物模型，为溶血性高胆红素血症相关研究提供实验基础模型。方法16只3日龄新生猕猴按随机数字法分为实验组和对照组，每组8只。实验组新生猕猴静脉注射质量分数为50mg／kg的10g／L盐酸苯肼溶液，对照组新生猕猴静脉注射9g／L盐水，分别于静脉注射后24、48h测定血胆红素及血红蛋白水平；使用监控设备记录猕猴临床表现；对实验组l例死亡猕猴脑组织行HE染色观察病理变化。结果实验组新生猕猴静脉注射盐酸苯肼溶液后出现不同程度的肤色灰暗、黏膜黄染和及尿液颜色加深，对照组未出现溶血及黄疸现象。实验组血清总胆红素[（252．76±63．42）μmol／L]、未结合胆红素[（165．85＋44．93）μmol／L]、结合胆红素[（87．16±21．22）μmol／L]水平明显高于对照组[（20．62±5．72）μmol／L、（7．93±2．31）μmol／L、（12．51±3．53）μmol／L]，差异均有统计学意义（t=14．581、13．881、14．040，P均〈0．01）；实验组血红蛋白水平[（47．18±10．09）μmol／L]明显低于对照组[（136．85±13．48）μmo]／L]，差异有统计学意义（t=-21．308，P〈0．01）。脑组织病理示实验组新生猕猴脑基底核胆红素沉积，脑细胞水肿、破裂及嗜酸性改变，严重部位出现细胞坏死。实验组猕猴出现不同程度的运动发育落后及协调性障碍，但在4个月后又逐渐恢复正常。结论静脉注射盐酸苯肼能够制作出符合人类新生儿溶血性高胆红素血症临床特征的猕猴动物模型。

Objective To establish the newborn rhesus monkey model of hemolytic hyperbilirubinemia and provide an experimental basic model for research of hyperbilirubinemia. Methods Sixteen 3 - day old newborn rhesus monkeys were divided into experimental group and control group, with 8 newborn rhesus monkeys in each group. Eight newborn rhesus monkeys in experimental group were treated with intravenous injection of 10 g/L phenylhydrazine hydrochloride（50 mg/kg） to establish model of homolytic hyperbilirubinemia. The newborn rhesus monkeys in control group were treated with intravenous injection of 9 g/L saline at the same time. Twenty - four hours and 48 hours after the experimental treatment, the bilirubin in blood was detected to evaluate the models, and the clinical manifestations of newborn rhesus monkeys with hyperbilirubinemia were recorded by using monitoring equipment. The brain slices were made to evaluate the model in 1 dead monkeys of experimental group. Results The newborn rhesus monkey of experi- mental group showed obvious skin, sclera jaundice and hemoglobinuria. The serum total bilirubin [ （252.76 ± 63.42） μmol/L ], unconjugated bilirubin [ （ 165.85 ± 44.93 ） μmol/L ] and conjugated bilirubin [ （ 87.16 ± 21.22 ） μmol/L ] in the experimental group were significantly higher than those [ （20.62 ± 5.72 ） μmol/L, （ 7.93 ± 2.31 ） μmol/L, （ 12.51 ± 3.53 ） μmol/L] in the control group,and the differences were statistically significant （ t = 14. 581,13. 881, 14.040, all P 〈 0.01 ）. The level of hemoglobin [ （47.18 ± 10.09） μmol/L] in the experimental group was signifi- cantly lower than that of the control group [ （ 136.85 ± 13.48） μmol/L], and the difference was statistically significant （ t = - 21. 308 ,P 〈 0.01 ）. The results of pathological showed brain edema, rupture and eosinophilic and bilirubin depo- sition in the basal nuclei, and necrosis appeared in some severe parts. And there were different degrees of retardation and coordination disorders in the experimental group~ newborn rhesus monkeys, but gradually returned to normal in 4 months later. Conclusion Intravenous injection of phenylhydrazine hydrochloride can be used to produce newborn rhe- sus monkey models of hemolytic hyperbilirubinemia.