Sijunzi decoction may decrease apoptosis via stabilization of the extracellular matrix following cerebral ischaemia-reperfusion in rats

Ping Yang; Ye-Mei Tian; Wen-Xiang Deng; Xiong Cai; Wang-Hua Liu; Liang Li; Hui-Yong Huang

doi:10.3892/etm.2019.7878

Sijunzi decoction may decrease apoptosis via stabilization of the extracellular matrix following cerebral ischaemia-reperfusion in rats

Exp Ther Med. 2019 Oct;18(4):2805-2812. doi: 10.3892/etm.2019.7878. Epub 2019 Aug 13.

Authors

Ping Yang¹, Ye-Mei Tian², Wen-Xiang Deng², Xiong Cai², Wang-Hua Liu², Liang Li^{2

3}, Hui-Yong Huang²

Affiliations

¹ Department of Psychiatry, Brains Hospital of Hunan Province, Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.
² Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China.
³ Key Discipline of Anatomy and Histoembryology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, P.R. China.

Abstract

Neurons undergo degeneration, apoptosis and death due to ischaemic stroke. The present study investigated the effect of Sijunzi decoction (SJZD), a type of traditional Chinese medicine known as invigorating spleen therapy, on anoikis (a type of apoptosis) in rat brains following cerebral ischaemia-reperfusion. Rats were randomly divided into sham, model, nimodipine and SJZD low/medium/high dose groups. A middle cerebral artery occlusion model was established. Neurobehavioural scores were evaluated after administration for 14 days using a five-grade scale. Blood-brain barrier permeability and apoptotic rate were detected using Evans blue (EB) extravasation and TUNEL staining, respectively. Tissue inhibitor of metalloproteinase 1 (TIMP-1), matrix metalloproteinase 9 (MMP-9) and collagen IV (COL IV) were determined using immunohistochemistry. Neurobehavioural scores decreased remarkably in all SJZD and nimodipine groups compared to the model group (P<0.05). Compared with the sham group, EB extravasation was higher in the model group (P<0.01). The amount of EB extravasation decreased in the SJZD high dose and nimodipine groups compared to the model group (P<0.01), and extravasation in the SJZD high dose group was lower than the SJZD low and medium dose groups (P<0.01). TIMP-1 and MMP-9 expression and apoptotic rate increased, but COL IV decreased significantly in the hippocampus of the model group compared to the sham group (P<0.01). TIMP-1 and COL IV expression increased significantly and MMP-9 and apoptotic rate decreased remarkably in all SJZD and nimodipine groups compared to the model group (P<0.01). TIMP-1 and COL IV expression decreased, but MMP-9 expression and apoptotic rate increased in the SJZD low and medium dose groups compared to the SJZD high dose group (P<0.01). SJZD rescued neurons and improved neurobehavioural function in rats following cerebral ischaemia-reperfusion, especially when used at a high dose. The mechanism may be related to protection of the extracellular matrix followed by anti-apoptotic effects.

Keywords: Sijunzi decoction; apoptosis; cerebral ischaemia-reperfusion; collagen IV; extracellular matrix; matrix metalloproteinase 9; tissue inhibitor of metalloproteinase 1.