Berberine alleviates cerebral ischemia-reperfusion injury in type 2 diabetic rats by inhibiting endoplasmic reticulum stress-related inflammatory pathways / 中华老年医学杂志

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-a)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 678 Glucoseregulated protein(GRP78)、Pancreatic endoplasmic reticul um 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.