新生儿缺氧缺血性脑损伤亚低温干预大鼠模型的建立

Establishment of a Model of Hypothermia Intervention after HypoxicIschemic Brain Damage in Newborn Rats

为探讨不同疗程亚低温对新生儿脑损伤的保护作用，建立新生儿缺血缺氧性脑损伤亚低温干预大鼠模型。先在７日龄清洁级ＳＤ大鼠上以右颈总动脉结扎术和吸入低氧浓度气体法制备缺血缺氧性脑损伤（ＨＩＢＤ）模型，再将其随机分为室温恢复组（ＲｏＴ组，ｎ＝４４）和３种疗程（２４ｈ，４８ｈ，７２ｈ）的亚低温干预组（Ｈｙ２４组，ｎ＝２６；Ｈｙ４８组，ｎ＝１４；Ｈｙ７２组，ｎ＝２０）。亚低温干预期间采用配方奶喂养，并监测脑温、血糖、血气和血浆乳酸水平。实验２周后以体重增加百分率（ＷＩＰ）、脑组织病变情况（右侧脑损伤分数和右侧海马细胞死亡率）判定疗效。结果，配方奶喂养的亚低温干预组的血糖维持在正常范围内（＞３ｍｍｏｌ／Ｌ），脑温降低４～５℃；ＨＩＢＤ后各组均出现酸中毒，ＨＩＢＤ后６ｈＲｏＴ组的血气和血乳酸水平仍明显增高，而亚低温组已恢复正常。实验２周后Ｈｙ２４组的ＷＩＰ明显高于ＲｏＴ组（分别为１３４．５％、８８．０％，Ｐ＜０．０１），Ｈｙ４８与ＲｏＴ组之间无明显差异（Ｐ＞０．０５）。病理学检查结果显示２４～７２ｈ的亚低温干预使脑损伤程度降低了５３％～８９％，Ｈｙ７２组疗效最佳。这表明新生儿ＨＩＢＤ亚低温干预大鼠模型已成功建立，ＨＩＢＤ后?

To establish the models of moderate hypothermia intervention after hypoxi cischemic brain damage (HIBD) in newborn rats,the posthypoxicischemi c 7dayold rats,weighing 14g±2g,were divided into 4 groups.The rats in gro up 1～3 (i.e.Hy24 group,n=26;Hy48 group,n=14;Hy72 group, n=20) were placed in water bath stabilized at 29℃ for 24 h,48 h,and 72 h respectively and fed with formular milk at the same time,and those in grou p 4 (RoT group,n=44) were stayed in a breeding room (25～29℃) with dams.After the insult,the levels of blood glucose,blood gas and plasma lactate w ere monitored.Two weeks after HIBD,body weight increase percents (WIP),right bra in injury scores (BIS) and percents of necrotic neurons in right hippocampus (HN NP) were determined.The results showed that the levels of blood glucose in the a nimal s fed with formular milk for 72 h were kept at normal levels (>3 mmol/L),and the brain temperatures were decreased by 4～5℃ after hypothermia intervention. At 6h after HIBD there were hypoxemia and metabolic acidosis in RoT group,but i n Hy24 group all rats recovered with nearly normal levels of blood gas and plasm a lactate.Two weeks after HIBD,WIP was significantly lower in RoT group than in Hy24 group (88.0% vs 134.5%,P<0.01),and not different between Hy48 and RoT groups (P>0.05).The results of neuropathological observati on of the brains indicated that BIS and HNNP in Hy groups were significantly red uced by 53%～89% with 24 h to 72 h hypothermia intervention,especially in Hy72 g roup,as compared to RoT group.The authors provided successful model of hypother mia intervention after HIBD in newborn rat by formular milk feeding,and found th at the optimal effects of moderate hypothermia intervention after HIBD were rea ched when the intervention lasted 72h and made the brain temperature decreased b y 4～5℃.