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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.
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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.
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Objective To investigate the effect of Berberine on insulin resistance and its mechanism in Otsuka Long-Evans Tokushima Fatty(OLETF) rats with metabolic syndrome(MS).Methods LETO(Long-evans Tokushima Otsuka)rats(the control group receiving standard normal diet,n=10)and diabetic OLETF rats(the MS group receiving high-fat diet for 24 weeks,n=30).Rats in the MS group were randomly divided into 3 subgroups(n=10,each subgroup).Each subgroup was gavaged with normal saline,high-dose Berberine(100 mg · kg-1 · d-1)and low-dose Berberine (50 mg · kg-1 · d-1) respectively,and the high-fat diet remained unchanged.After 6 weeks of berberine treatment,body weight,blood glucose and lipid metabolism parameters were determined.The oral glucose tolerance test(OGTT) and insulin tolerance test(ITT) were used to detect insulin resistance.Expression levels of the protein and mRNA of 78 kDa glucose-regulated protein (GRP7 8),Caspase-12 and CCAAT/enhancer-binding protein(C/EBP) homologous protein(CHOP) in skeletal muscles were detected by Western blot and RT-PCR.Results After Berberine treatment,the body weight,fasting plasma glucose,fasting insulin[(28.9 ± 2.0) mU/L,(31.5± 2.4) mU/L vs.(36.9 ± 4.7) mU/L],total cholesterol,triglycerides,and low-density lipoprotein cholesterol were decreased,while the high-density lipoprotein cholesterol(HDL-C) levels were increased in MS rats with high-dose berberine and low-dose berberine as compared with the control group (P ＜ 0.05) respectively.Berberine treatment could reduce the protein and mRNA expression levels of GRP78,Capase-12 and CHOP in the skeletal muscle of MS rats(P＜0.05).Conclusions Berberine may alleviate insulin resistance in rats with metabolic syndrome by reducing endoplasmic reticulum stress in skeletal muscle.
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Objective: This work aimed to construct stable MCF-7 cell sublines from which staphylococcal nuclease domain con-taining 1 (SND1) expression was interfered to analyze the effect of SND1 silencing on the proliferation and metastasis of MCF-7 cells. Methods: The lentivirus that could mediate SND1 silencing was prepared. MCF-7 cells were infected with the lentiviruses to construct stable sub-cell lines. Quantitative real-time polymerase chain reaction and Western blot analysis were employed to determine SND1 ex-pression level. MTS, wound healing, and transwell assays were applied to analyze the effect of SND1 silencing on the proliferation, mi-gration, and invasion of MCF-7 cells. Results: A lentivirus expression vector that contains sequences encoding shRNAs targeting SND1 and an shRNA negative control were successfully established. The lentiviruses (LV-SH1, LV-SH2, LV-SH3, and 和 LV-NC) were then collected and packaged. Stabilized MCF-7 sublines were prepared through infection with lentiviruses. The most efficient MCF-7 stable cell subline, MCF-SH3, was selected for SND1 silencing. Compared with the control cell, the proliferation, migration, and inva-sion potential of MCF-SH3 were significantly decreased. Conclusion: SND1 could promote the proliferation, migration, and invasion of breast cancer cells. Thus, silencing SND1 expression will inhibit such proliferation, migration, and invasion. These results indicated that the unusual expression of SND1 is associated with breast cancer and may participate in cancer progression by affecting prolifera-tion, migration, and invasion.