Abstract：【Objective】To investigate the effect of fasudil on autophagy in hippocampal CA1 region and mTOR pathway in rats with subarachnoid hemorrhage (SAH). 【Methods】Eighteen SPF male SD rats were randomly divided into sham operation group (SHAM group,n=6), SAH group (n=6) and fasudil group (FAS group,n=6). In FAS group, fasudil hydrochloride 10 mg/(kg?d) was injected intraperitoneally for 3 days; the SHAM group and the SAH group were intraperitoneally injected with the same amount of normal saline at the same time, and the rats in the sham group did not puncture the blood vessels. Shuttle box test was used to detect the learning and memory ability of rats in each group; Hematoxylin eosin (HE) staining was used to observe the pathological changes of neurons in hippocampal CA1 area of rats in each group, and the number of normal neurons was calculated; The changes of autophagy protein [tube associated protein light chain 3 (LC3), silkworm isolate protein 1 (p62)] and phosphoinositide 3-kinase/mammalian rapamycin target protein (PI3K/mTOR) pathway proteins [PI3K, p-PI3K, mTOR, p-mTOR] in hippocampal CA1 region of rats in each group were detected by Western blotting. 【Results】The escape times of the sham group, the SAH group and the FAS group were (26.33±3.05), (18.52±2.03), (22.06±2.58) times, the escape time was (3.69±1.01) s, (8.77± 3.96) s and (6.05±2.51) s, and the number of normal nerve cells was (125.69±18.85), (63.03± 9.46) and (95.77±14.33) respectively, The ratio of LC3-Ⅱ/LC3-Ⅰ was (0.97±0.15)%, (0.38±0.06)%, (0.56±0.09)%, the expression of p62 protein was (0.45±0.07), (1.13±0.17), (0.81±0.13), p-PI3K/PI3K protein was 0.65±0.09,1.58±0.24, 1.03±0.15, p-mTOR/mTOR was 0.73±0.10,1.36±0.20,1.11±0.17, respectively. Compared with the sham group, the number of escape reaction, the number of normal nerve cells in CA1 area, the ratio of LC3-Ⅱ/LC3-Ⅰand the level of p-PI3K/PI3K protein in the SAH group and the Fas group decreased or reduced (P<0.05), the escape reaction time and the levels of p62 protein and p-mTOR/mTOR protein in CA1 area increased or promoted (P<0.05), However, the number of escape reaction, the number of normal nerve cells in CA1 area, the ratio of LC3-Ⅱ/LC3-Ⅰand the level of p-PI3K/PI3K protein in the fasudil group were higher or more than those in the SAH group (P<0.05), and the escape reaction time and the levels of p62 protein and p-mTOR/mTOR protein in CA1 area were lower or lower than those in the SAH group (P<0.05). 【Conclusion】Fasudil can enhance the autophagy of neurons in hippocampal CA1 region of SAH rats, protect cells, and then enhance the learning and memory function of rats. The mechanism may be realized by inhibiting the activation of PI3K/mTOR pathway.
曹宏斌, 冯乐霄. 法舒地尔对蛛网膜下腔脑出血大鼠海马CA1区自噬作用及对mTOR通路的影响[J]. 医学临床研究, 2022, 39(1): 18-22.
CAO Hong-bin, Feng Le-xiao. Effect of Fasudil on Autophagy in Hippocampal CA1 Region and mTOR Pathway in Rats with Subarachnoid Hemorrhage. JOURNAL OF CLINICAL RESEARCH, 2022, 39(1): 18-22.
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2022, Vol. 39 
