文章摘要
竹节参皂苷对异氟醚所致发育期大鼠神经毒性和认知功能的影响
Effect of chikusetsu saponin IVa on isoflurane-elicited neurotoxicity and cognitive deficits in developmental rats
  
DOI：10.12089/jca.2018.08.016
中文关键词: 竹节参皂苷  异氟醚  发育期  神经毒性  认知功能
英文关键词: Chikusetsu saponin IVa  Isoflurane  Developmental period  Neurotoxicity  Cognition
基金项目:国家自然科学基金(81571047, 81400882, 81500931)
作者单位E-mail
方茜 430030,武汉市,华中科技大学同济医学院附属同济医院麻醉科  
高杰 430030,武汉市,华中科技大学同济医学院附属同济医院麻醉科  
李世勇 430030,武汉市,华中科技大学同济医学院附属同济医院麻醉科  
张杰 430030,武汉市,华中科技大学同济医学院附属同济医院麻醉科  
杨春 430030,武汉市,华中科技大学同济医学院附属同济医院麻醉科  
罗爱林 430030,武汉市,华中科技大学同济医学院附属同济医院麻醉科 alluo@tjh.tjmu.edu.cn 
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中文摘要:
      
目的 探讨竹节参皂苷对异氟醚所致发育期大鼠海马神经毒性及认知功能的影响。

方法 7日龄SD大鼠60只,雌雄不限,体重20～25 g,随机分为四组(n=15)。对照组(Con组):吸入对照气(空气)6 h;异氟醚组(Iso组):吸入1.8%异氟醚6 h;竹节参皂苷+异氟醚组(Iso+ChIV组):麻醉前30 min腹腔注射竹节参皂苷30 mg/kg后吸入1.8%异氟醚6 h;竹节参皂苷(ChIV组):麻醉前30 min腹腔注射竹节参皂苷30 mg/kg后吸入对照气(空气)6 h。麻醉结束后12 h取海马组织检测突触后致密蛋白95(PSD95)、突触素I(Synapsin I)、B淋巴细胞瘤2相关X蛋白(Bax)、B淋巴细胞瘤2(Bcl-2)蛋白含量,TUNEL染色检测神经元凋亡情况,测定乳酸脱氢酶(LDH)活性。于出生后第31～35天采用水迷宫评估空间学习记忆能力。

结果 与Con组比较,Iso组PSD95、Bcl-2蛋白含量明显降低,Bax蛋白含量明显升高,TUNEL阳性细胞数明显增多,LDH活性明显增强(P< 0.05);与Iso组比较,Iso+ChIV组PSD95、Bcl-2蛋白含量明显升高,Bax蛋白含量明显降低,TUNEL阳性细胞数明显减少,LDH活性明显减弱(P< 0.05)。与Con组比较,Iso组第34和35天逃避潜伏路线明显延长(P< 0.05),第33、34和35天逃避潜伏期明显延长(P< 0.05),第35天目标象限停留时间明显缩短，平台穿越次数明显减少(P< 0.05)。与Iso组比较,Iso+ChIV组第34和35天逃避潜伏路线明显缩短，逃避潜伏期明显缩短(P< 0.05),第35天目标象限停留时间明显延长，平台穿越次数明显增多(P< 0.05)。

结论 竹节参皂苷可明显改善异氟醚所致发育期大鼠神经毒性和认知功能,其机制可能与抑制发育期神经凋亡有关。
英文摘要:
      
Objective To investigate the effect of chikusetsu saponin IVa (ChIV) on isoflurane-induced hippocampal neurotoxicity and developmental cognitive deficits in developmental rats.

Methods Sixty SD pup rats, 7 days old, weighing 20-25 g, were randomly assigned into 4 groups (n=15 per group): control group (group Con), isoflurane group (group Iso), ChIV+isoflurane group (group Iso+ChIV), and ChIV group (group ChIV). Rats in group Con were exposured to control gas (air) for 6 h, while rats in group Iso were exposured to 1.8% isoflurane for 6 h. ChIV 30 mg/kg was injected intraperitoneally 30 min prior to 1.8% isoflurane anesthesia in group Iso+ChIV. ChIV 30 mg/kg was injected intraperitoneally 30 min prior to control gas (air) exposure for 6 h. Hippocampal tissues of rats were harvested 12 h after the end of isoflurane anesthesia for measurement of post synaptic density-95 (PSD95), Synapsin I, B cell lymphoma associated X protein (Bax) and B cell lymphoma/lewkmia-2 (Bcl-2). Hippocampal neuron apoptosis was measured by TUNEL assay. Morris water maze for evaluation of cognitive function was performed 35 after birth.

Results Compared with group Con, the expression of PSD95 and Bcl-2 reduced significantly, the expression of Bax increased significantly, TUNEL positive cells increased significantly, the LDH activity increased significantly in group Iso (P< 0.05). Compared with group Iso, the expression of PSD95 and Bcl-2 increased significantly, the expression of Bax reduced significantly, TUNEL positive cell decreased significantly, the LDH activity reduced significantly in group Iso+ChIV (P< 0.05). Compared with group Con, the escape latency increased significantly on day 34 and 35, and the escape path length increased significantly on day 33 - 35 in group Iso (P< 0.05). The platform crossing and time spend in target quarter reduced significantly on day 35 in group Iso (P< 0.05). Compared with group Iso, the escape latency and escape path length reduced significantly on day 34 and 35, the platform crossing and time spend in target quarter increased significantly on day 35 in group Iso+ChIV (P< 0.05).

Conclusion Chikusetsu saponin IVa could ameliorate isoflurane-induced neurotoxicity and cognitive dysfunction in developmental rats, while the underline mechanism is likely associated with its inhibitory effects on apoptosisin devenopmental neurons.
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