Teng Fei, Yin Yanxin, Guo Jia, Jiang Ming
Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Biomedical Research Center of Tongji University Suzhou Institute, Suzhou, Jiangsu 215101, P.R. China.
Exp Ther Med. 2020 Apr;19(4):2433-2440. doi: 10.3892/etm.2020.8510. Epub 2020 Feb 10.
Calpain activation may have an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). The present study investigated the effects of the calpastatin peptide, a cell-permeable peptide that functions as a potent inhibitor of calpain, on EBI in a rat SAH model. It was revealed that calpastatin peptide treatment significantly reduced SAH-induced body weight loss and neurological deficit at 72 h when compared with untreated SAH controls. Furthermore, the quantification of brain water content and the extravasation of Evans blue dye revealed a significant reduction in SAH-induced brain edema and blood-brain barrier permeability at 72 h due to treatment with the calpastatin peptide when compared with untreated SAH controls. Finally, calpastatin peptide treatment significantly attenuated the protein levels of Bax, cytochrome c, cleaved caspase-9 and cleaved caspase-3, and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labelling-positive cells in the basal cortex at 72 h after SAH when compared with untreated SAH controls. These results indicated that the calpastatin peptide may ameliorate EBI following SAH in rat models.
钙蛋白酶激活可能在蛛网膜下腔出血（SAH）后的早期脑损伤（EBI）中起重要作用。本研究在大鼠SAH模型中，研究了钙蛋白酶抑制蛋白肽（一种可穿透细胞的肽，作为钙蛋白酶的有效抑制剂发挥作用）对EBI的影响。结果显示，与未治疗的SAH对照组相比，钙蛋白酶抑制蛋白肽治疗在72小时时显著减轻了SAH诱导的体重减轻和神经功能缺损。此外，脑含水量的定量分析和伊文思蓝染料的外渗显示，与未治疗的SAH对照组相比，由于钙蛋白酶抑制蛋白肽治疗，在72小时时SAH诱导的脑水肿和血脑屏障通透性显著降低。最后，与未治疗的SAH对照组相比，钙蛋白酶抑制蛋白肽治疗在SAH后72小时时显著减弱了Bax、细胞色素c、裂解的半胱天冬酶-9和裂解的半胱天冬酶-3的蛋白水平，并减少了基底皮质中末端脱氧核苷酸转移酶dUTP缺口末端标记阳性细胞的数量。这些结果表明，钙蛋白酶抑制蛋白肽可能改善大鼠模型中SAH后的EBI。
