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

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.