目的 探讨红景天苷对缺血性脑卒中大鼠的神经保护作用机制及在TGF-β1/Smad3信号通路的调节机制。方法 将48只12～15周龄的SPF级SD雄性大鼠随机分为4组（n=12）：假手术组、模型组、红景天苷组（治疗组）、信号通路强化干预组（TGF-β1组）。模型组、治疗组、TGF-β1组采用线栓法建立永久性局灶脑缺血大鼠模型，假手术组不插尼龙线。造模手术前48 h，治疗组、TGF-β1组大鼠每天上午固定时间进行药物干预：治疗组以10 mg/kg红景天苷icv给药，TGF-β1组以20 mg/kg TGF-β1 icv给药，假手术组、模型组给予等体积的生理盐水，连续给药14 d后，将各组大鼠施以断头处死。分别采用TTC染色、尼氏染色、TUNEL染色、免疫荧光、Western blotting法检测各组大鼠脑梗死体积、完整神经元数目、细胞凋亡，以及Bax、Bcl-2、TGF-β1、p-Smad3的蛋白表达水平；电镜观察各组大鼠脑组织的超微结构的改变。结果 与假手术组相比，模型组大鼠脑梗死体积明显增大，脑组织中完整的神经元数量明显减少，神经细胞凋亡率明显升高，Bax的表达明显升高，Bcl-2的表达明显降低，TGF-β1、p-Smad3的表达明显升高，差异有统计学意义（P<0.05）；电镜下观察模型组大鼠大脑超微结构破坏严重，缺血性脑卒中病理症状明显。与模型组相比，治疗组、TGF-β1组大鼠脑梗死体积明显减少，脑组织中完整的神经元数量明显增多，神经细胞凋亡率明显降低，Bax的表达明显降低，Bcl-2的表达明显升高，TGF-β1、p-Smad3的表达明显升高，差异有统计学意义（P<0.05）；电镜下观察治疗组大鼠大脑超微结构缺血性脑卒中病理症状明显减轻；治疗组和TGF-β1组相比，观察指标差异不显著（P>0.05）。结论 红景天苷可以激活缺血性脑卒中后的TGF-β1/Smad3信号通路，从而减轻神经功能损害，发挥对神经细胞的保护作用。

Objective To investigate the neuroprotective mechanism of salidroside after ischemic stroke and its regulation mechanism in TGF-β1/Smad3 signaling pathway. Methods A total of 48 SPF SD male rats aged 12-15 weeks were randomly divided into four groups (n=12):Sham-operated group (sham group), model group, salidroside group (treatment group), and signaling pathway-enhanced intervention group (TGF-β1 group). In the model group, treatment group, and TGF-β1 group, a permanent focal cerebral ischemia rat model was established by suture method, and the sham group was not inserted with nylon thread. 48 h before the modeling operation, the treatment group and the TGF-β1 group were given drug intervention at a fixed time every morning:the treatment group was administered with 10 mg/kg salidroside ventricle, and the TGF-β1 group was treated with 20 mg/kg TGF-β1. The intraventricular injection was administered, and the sham group and the model group were given an equal volume of physiological saline. After 14 d of continuous administration, each group of rats was sacrificed by decapitation. TTC staining, Nissl staining, TUNEL staining, immunofluorescence, and Western blot were used to determine the infarct volume, the number of intact neurons, the cell apoptosis, the expression of Bax and Bcl-2 expression, the expression levels of Bax, Bcl-2, TGF-β1, and p-Smad3. The ultrastructural changes of brain tissue were observed by electron microscopy. Results Compared with the sham group, the cerebral infarction volume of the model group was significantly increased, the number of intact neurons in the brain tissue was significantly reduced, the apoptosis rate of nerve cells was significantly increased, and the expression of Bax was significantly increased, the expression of Bax was significantly decreased. The expression of TGF-β1 and p-Smad3 was significantly increased, and the difference was statistically significant (P<0.05). Under the electron microscope, the ultrastructural damage of the brain in the model group was severe, and the pathological symptoms of ischemic stroke were obvious; Compared with the model group, the cerebral infarction volume of the treatment group and the TGF-β1 group was significantly reduced, the number of intact neurons in the brain tissue was significantly increased, the apoptosis rate of nerve cells was significantly decreased, the expression of Bax was significantly decreased, and the expression of Bcl-2 was significantly increased. The expression of TGF-β1 and p-Smad3 was significantly increased, and the difference was statistically significant (P<0.05). The pathological symptoms of ultrastructural ischemic stroke in the model group were significantly reduced under electron microscope. The differences of the observation indexes between TGF-β1 group and treatment group were not obvious, and it was not statistically significant (P>0.05). Conclusion Salidroside can activate the TGF-β1/Smad3 signaling pathway after ischemic stroke, thereby alleviating neurological damage and exerting protective effects on nerve cells.

R285.5

贵州省中药管理局项目（QZYY2017-039）