小檗碱对氧糖剥夺/复氧诱导的大鼠体外血脑屏障损伤的保护作用

Abstract
Figure/Table
References (20)
Related Citation (15)

Download: PDF (849 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective To investigate the protective effect of berberine on oxygen glucose deprivation/reoxygenation (OGD/R) induced blood-brain barrier injury in vitro in rats and its mechanism. Methods Primary cultured rat brain microvascular endothelial cells (rBMECs) were divided into the control group, the model group and the berberine administration group. Fresh medium was added to the control group. The model group and the berberine administration group were preincubated with berberine at different concentrations (0, 1, 3, 10, 30, 100 μmol/L) for 24 h, then the low glucose medium was replaced and the culture medium was placed in a three-gas incubator without oxygen (95%N2/5%CO2) for 2 h (oxygen glucose deprivation, OGD). then replaced with fresh medium, at 37℃ and 5%CO2 incubator continue to develop 2 h (Reoxygenation, R). Cell survival was determined by MTT assay, cell tightness was determined by transendothelial electrical resistance, protein expression levels of tight junction protein ZO-1, occludin and nuclear factor-κB p65 (NF-κB p65) were detected by Western blot assay, and levels of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA assay. Results Compared with the the control group, rBMECs cell survival rate, ZO-1 expression level and occludin expression level in the model group were significantly reduced, transendothelial electrical resistance showed a decreasing trend, and NF-κB p65 expression level, IL-1β, and TNF-α levels were significantly increased in the model group, the differences were highly statistically significant (all P ＜ 0.01). Compared with the model group, the survival rate of rBMECs cells in the berberine administration group increased to different degrees, the ZO-1 expression, occludin expression, the transmembrane electrical resistance increased significantly in the berberine 10 and 30 μmol/L concentration groups, with statistically significant differences (P ＜ 0.05 or P ＜ 0.01). Meanwhile, the NF-κB p65 expression and the levels of IL-1β and TNF-α were significantly decreased in the berberine 10 and 30 μmol/L concentration groups, the differences were highly statistically significant (all P ＜ 0.01). Conclusion Berberine plays a protective role of blood brain barrier on OGD/R injury by inhibiting NF-κB entry into the nucleus, reducing the release of inflammatory factors, and improving the damage of OGD/R-induced rBMECs.

Key words： Berberine Blood-brain barrier Nuclear factor-κB p65 Inflammation

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	WANG Meihua WANG Jia HAN Dan WANG Yu

Cite this article:

WANG Meihua WANG Jia HAN Dan WANG Yu. Protective effect of berberine on in vitro blood-brain barrier injury induced by oxygen glucose deprivation/reoxygenation in rats[J]. 中国医药导报, 2020, 17(9): 16-20.

URL:

http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2020/V17/I9/16

[1] Vidale S，Consoli A，Arnaboldi M，et al. Postischemic Inflammation in Acute Stroke [J]. J Clin Neurol，2017，13（1）：1-9.
[2] Li Y，Zhong W，Jiang Z，et al. New progress in the approaches for blood-brain barrier protection in acute ischemic stroke [J]. Brain Res Bull，2019，144：46-57.
[3] Ji B，Zhou F，Han L，et al. Sodium Tanshinone IIA Sulfonate Enhances Effectiveness Rt-PA Treatment in Acute Ischemic Stroke Patients Associated with Ameliorating Blood-Brain Barrier Damage [J]. Transl Stroke Res，2017， 8（4）：334-340.
[4] Wu W，Zhong W，Lang B，et al. Thrombopoietin could protect cerebral tissue against ischemia-reperfusion injury by suppressing NF-kappaB and MMP-9 expression in rats [J]. Int J Med Sci，2018，15（12）：1341-1348.
[5] Jiang X，Andjelkovic AV，Zhu L，et al. Blood-brain barrier dysfunction and recovery after ischemic stroke [J]. Prog Neurobiol，2018，163-164：144-171.
[6] Kumar A，Ekavali，Chopra K，et al. Current knowledge and pharmacological profile of berberine：An update [J]. Eur J Pharmacol，2015，761：288-297.
[7] Ahmed T，Gilani AU，Abdollahi M，et al. Berberine and neurodegeneration：A review of literature [J]. Pharmacol Rep，2015，67（5）：970-979.
[8] Pang B，Zhao LH，Zhou Q，et al. Application of berberine on treating type 2 diabetes mellitus [J]. Int J Endocrinol，2015，2015：905749.
[9] Xue Y，He JT，Zhang KK，et al. Methamphetamine reduces expressions of tight junction proteins，rearranges F-actin cytoskeleton and increases the blood brain barrier permeability via the RhoA/ROCK-dependent pathway [J]. Biochem Biophys Res Commun，2019，509（2）：395-401.
[10] Lv J，Hu W，Yang Z，et al. Focusing on claudin-5：A promising candidate in the regulation of BBB to treat ischemic stroke [J]. Prog Neurobiol，2018，161：79-96.
[11] Haley MJ，Lawrence CB. The blood-brain barrier after stroke：Structural studies and the role of transcytotic vesicles [J]. J Cereb Blood Flow Metab，2017，37（2）：456-470.
[12] Abbott NJ，Patabendige AA，Dolman DE，et al. Structure and function of the blood-brain barrier [J]. Neurobiol Dis，2010，37（1）：13-25.
[13] Sandoval KE，Witt KA. Blood-brain barrier tight junction permeability and ischemic stroke [J]. Neurobiol Dis，2008， 32（2）：200-219.
[14] Zhou YF，Li YN，Jin HJ，et al. Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats [J]. FASEB J，2018， 32（4）：2181-2196.
[15] Abdullahi W，Tripathi D，Ronaldson PT. Blood-brain barrier dysfunction in ischemic stroke：targeting tight junctions and transporters for vascular protection [J]. Am J Physiol Cell Physiol，2018，315（3）：C343-C356.
[16] Jin R，Liu L，Zhang S，et al. Role of inflammation and its mediators in acute ischemic stroke [J]. J Cardiovasc Transl Res，2013，6（5）：834-851.
[17] Li X，Su L，Zhang X，et al. Ulinastatin downregulates TLR4 and NF-kB expression and protects mouse brains against ischemia/reperfusion injury[J]. Neurol Res，2017， 39（4）：367-373.
[18] Simmons LJ，Surles-Zeigler MC，Li Y，et al. Regulation of inflammatory responses by neuregulin-1 in brain ischemia and microglial cells in vitro involves the NF-kappa B pathway [J]. J Neuroinflammation，2016，13（1）：237.
[19] Gao S，Mo J，Chen L，et al. Astrocyte GGTI-mediated Rac1 prenylation upregulates NF-kappaB expression and promotes neuronal apoptosis following hypoxia/ischemia [J]. Neuropharmacology，2016，103：44-56.
[20] Chen AQ，Fang Z，Chen XL，et al. Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke [J]. Cell Death Dis，2019，10（7）：487.