丹参酮IIA对慢性肾功能衰竭大鼠认知障碍的神经保护作用及其机制

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Abstract Objective: To investigate the neuroprotective effect and the potential mechanism of Tan IIA on the cognitive impairment in chronic renal failure (CRF) rats. Methods: Sixty male SD rats were randomly divided into 5 groups with 12 rats in each group. They were grouped as follows: the control group, the model group, the TM group, the TM+Tan IIA group, and the Tan IIA group. The 5/6 renal excision method were adopted to simulate the CRF model. From the 4th weeks to 12th weeks, the TM group and the TM+Tan IIA group were injected TM intra-peritoneal twice per week with the dosage of 4.5 mg/kg, meanwhile the TM+Tan IIA group and the Tan IIA group were injected Tan IIA intraperitoneally once daily with the dosage of 15 mg/kg. The control group was injected intra-peritoneat with an equal volume of saline. Morris water maze test was applied to test the learning and memory abilities of the rats after modeling. HE staining was used to observe the morphology of hippocampal neurons. Tunel staining was used to detect the apoptosis index of hippocampal neurons. MDA content and SOD activity in Serum and hippocampal tissues were detected by the kit. Western blot was used to detect the expression of GRP78, CHOP and Caspase-12 proteins. Results: Compared with the control group, the learning and memory abilities of the model rats in the Morris water maze were significantly decreased, and the decline was more obvious after the TM intervention. Meanwhile, the level of GRP78, CHOP, Caspase-12 protein expressions and the percentage of apoptotic cells increased, accompanied with the increased MDA content reduced SOD levels and disrupted cell structure. In the ERS agonist TM intervention group, increased ERS-associated apoptosis, increased oxidative stress levels, and more pronounced cell structure destruction were observed compared with the model group. The Tan IIA intervention significantly decreased the expression of ERS-associated apoptosis, increased the ability of anti-oxidative stress, and significantly ameliorated the cell structure. Moreover the learning and memory ability of the rats in the Morris water maze was significantly improved. Conclusion: The ERS related excessive apoptosis may be involved in CRF-induced cognitive impairment in rats. Tan IIA probably plays a role in neuroprotection and improves the cognitive function by inhibiting the ERS-related apoptosis and antioxidative stress.

Key words： tanshinone IIA kidney failure, chronic cognitive disorders endoplasmic reticulum stress oxidative stress rats

Received: 01 January 2018

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	ZHU Ming
	WANG Xiaotong
	MIN Jingjing
	CHEN Qi
	Wang Xiaoyi

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I7/517

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