红景天苷经自噬途径减少脑出血后继发神经损伤的的机制探讨

Mechanism of Salidroside Reducing Secondary Nerve Injury after Cerebral Hemorrhage through Autophagy Pathway

目的:探讨红景天苷对脑出血后继发神经损伤大鼠模型神经功能的调节作用及其机制探讨。方法:大鼠分为非模型组、模型组,模型组包括对照组、雷帕霉素组、红景天苷组、3-MA组。对大鼠进行神经功能NSS评分,病理组织学检测坏死细胞率、自噬小体,Western Blot检测LC3-Ⅰ、LC3-Ⅱ、Bcl-2、Bax的表达,Tunel法检测神经细胞凋亡。结果:造模后,雷帕霉素治疗后NSS评分明显下降至5.24±0.98(P<0.05),给予红景天苷治疗后下降至4.89±0.76(P<0.05);雷帕霉素组细胞坏死率为(29.21±11.90)%,自噬小体为(41.21±11.90)%,红景天苷组细胞坏死率为(34.21±9.45)%,自噬小体为(38.21±9.45)%,坏死率均较对照组减少(P<0.05),自噬小体较对照组增加(P<0.05);雷帕霉素及红景天苷组LC3-Ⅱ表达升高,LC3-Ⅱ/LC3-Ⅰ比值上升,Bcl-2表达增加,Bax表达降低;神经细胞凋亡率分别为23.15%及34.18%,均较对照组明显升高(P<0.05)。3-MA组神经功能NSS评分升高,坏死率增加,自噬小体减少, LC3-Ⅱ、Bcl-2的表达被抑制,LC3-Ⅰ、Bax表达升高,神经元凋亡率增加。结论:红景天苷可以改善脑出血后神经损伤大鼠模型的神经功能,其可能机制是通过激活自噬从而减少神经细胞坏死和凋亡达到减少神经损伤,达到保护脑神经的目的。

Objective:To investigate the regulation effect of salidroside on rat model of nerve injury after cerebral hemorrhage and explore its mechanism.Methods:The rats were divided into non-model group and model group.The model group included control group,rapamycin group,salidroside group and 3-MA group.NSS scores of neurological function were performed in rats.Pathological histology was used to detect the necrotic cell rate and autophagosomes.Western Blot was used to detect the expressions of LC3-I,LC3-II,Bcl-2 and Bax.Tunel assay was used to detect apoptotic cells.Results:After modeling,the NSS score of rapamycin decreased significantly to 5.24±0.98(P<0.05).After intervention with salidroside,it decreased to 4.89±0.76(P<0.05).The necrosis rate of rapamycin group cells was(29.21±11.90)%.The autophagosome was(41.21±11.90)%.The necrosis rate of salidroside group was(34.21±9.45)%.The autophagosome was(38.21±9.45)%and the necrosis rate was lower than that in the control group(P<0.05).Autophagy bodies increased compared with that of the control group(P<0.05).LC3-II expression increased in rapamycin and salidroside group.LC3-II/LC3-I ratio increased.Bcl-2 expression increased.Bax expression decreased.The rate of neuronal apoptosis was 23.15%and 34.18 which were significantly higher than those in the control group(P<0.05).In the 3-MA group,the neurological NSS score and necrosis rate were increased.The autophagy body was decreased and the expressions of LC3-II and Bcl-2 were inhibited.The expressions of LC3-I and Bax increased and the apoptosis rate of neurons was increased.Conclusion:Salidroside can improve the neurological function on rat models of neurological injury after cerebral hemorrhage.The possible mechanism is that salidroside can reduce neuronal necrosis and apoptosis by activating autophagy to reduce nerve injury and protect the cranial nerve.