Berberine alleviates cerebral ischemia-reperfusion injury in type 2 diabetic rats by inhibiting endoplasmic reticulum stress-related inflammatory pathways

Abstract

Objective To examine the effects of Berberine(BBR)on inflammatory pathways related to endoplasmic reticulum stress(ERS)in the penumbra area following focal cerebral ischemia-reperfusion injury in type 2 diabetic rats. Methods A total of 72 healthy male Sprague-Dawley rats were fed a high-fat, high-sugar diet and injected with streptozotocin to establish a type 2 diabetes mellitus model.The diabetic rats were randomly divided by digital lottery method into a Sham operation group(Sham group), a diabetic rat + BBR treatment group(BBR group), a diabetic middle cerebral artery occlusion(MCAO)model group(MCAO group), and a diabetic rats MCAO + BBR treatment group(MCAO + BBR group). Six rats were included in each group.The two treatment groups received prespecified doses of BBR through gastric perfusion at 48 h, 24 h before surgery, and 6h after surgery.The MCAO model was prepared by a suture occlusion method.The neurological deficit scores were performed, and the expression of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)was detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of ERS marker protein GRP78 was detected by quantitative real time polymerase chain reaction(RT-qPCR), and the expression of ERS-related inflammatory pathway proteins[78 Glucoseregulated protein(GRP78)、Pancreatic endoplasmic reticulum Rinase(PERK)、nuclear factor-κB(NF-κB)]was detected by Western blot. Results the cerebral ischemic penumbra area, after 2 h of ischemia and 24 h of reperfusion, the neurological deficit score in the MCAO group was higher than that in the MACO+ BBR group [(2.83±0.41)vs.(1.67±0.52), P<0.05], and the expression levels of pro-inflammatory cytokines(TNF-α and IL-1β)and ERS-related inflammatory pathway proteins(GRP78, PERK and NF-κB p65)were also significantly increased(all P<0.05). However, BBR treatment was able to alleviate the neurological dysfunction caused by cerebral ischemia-reperfusion in type 2 diabetic rats(P<0.05). Similarly, BBR treatment also reduced the expression levels of pro-inflammatory factors(TNF-α and IL-1β)and ERS-related inflammatory pathway proteins(GRP78, PERK and NF-κB p65)in the cerebral ischemic penumbra area(all P<0.05). Conclusions Through inhibiting ERS-related inflammatory pathways, BBR plays a neuroprotective role to alleviate cerebral ischemia-reperfusion injury in type 2 diabetic rats. Key words: Berberine; Inflammation; Diabetes, type 2; Brain ischemia