The Cerebroprotein Hydrolysate-I Plays a Neuroprotective Effect on Cerebral Ischemic Stroke by Inhibiting MEK/ERK1/2 Signaling Pathway in Rats

Yuqian Ren,1 Xiaoqing Ma,1 Tingting Wang,1 Baohe Cheng,2 Leiming Ren,3 Zehua Dong,4 Hongling Liu5 1Institute of Cerebrovascular Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 2Shandong Haoyun International Hospital of Stem Cells, Jinan, Shandong, 250001, People’s Republic of China; 3Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 4Department of Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China; 5Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaCorrespondence: Zehua Dong; Hongling Liu Tel +86-139 63958230; +86-18661808612Email gonewithwind18@163.com; lhl3798@126.comObjective: To investigate the neuroprotective effect and mechanism of cerebroprotein hydrolysate-I (CH-I) on cerebral ischemia/reperfusion injury in rats.Methods: A total of 100 adult healthy male SD rats were randomly divided into a sham group, model group, CH-I treated group, and cerebrolysin (CBL) positive group, consisting of 20 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model of rats was built by inserting a suture into the left external carotid artery (ECA) through the internal carotid artery (ICA). Treatment was performed by intraperitoneal injection of CH-I (20 mg/kg). The neurobehavioral function of rats was evaluated by modified neurological severity scores (mNSS). TTC staining was used to detect the cerebral infarction volume (CIV) of rats. The morphological and structural changes of nerve cells were observed by HE staining and the neuronal apoptosis was counted by TUNEL assay. Immunohistochemical (IHC) analysis was used to detect BDNF and pMEK1/2 expressions. The expressions of BDNF, pMEK1/2, pERK1/2, and pCREB were determined with Western blotting.Results: After treatment with CH-I, the mNSS and CIV of rats were improved (P< 0.05). And the CH-I can reduce the degeneration and apoptosis of nerve cells in rats (P< 0.01). Western blotting showed that the expressions of pMEK1/2, pERK1/2, and pCREB in rats were increased, while the expression of BDNF was decreased after modeling (P< 0.05). After treatment, the expressions of pMEK1/2, pERK1/2, and pCREB in the CH-I group were decreased (P< 0.05), while the expression of BDNF was significantly increased (P< 0.05) compared with the model group. IHC showed that the expression of BDNF and pMEK1/2 was consistent with Western blotting.Conclusion: It is suggested that the CH-I might play a neuroprotective role by inhibiting the expression of MEK-ERK-CREB and enhancing the expression of BDNF after cerebral ischemia/reperfusion injury, thus improving the neurobehavioral function of MCAO/R rats.Keywords: cerebroprotein hydrolysate-I, cerebral ischemia/reperfusion injury, apoptosis, MAPK/ERK1/2 signaling pathway, rats