Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats....Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.展开更多
神经退行性疾病是由神经元进行性丢失而引起的神经系统功能障碍。尽管该类疾病的发病机制尚不清楚,但近期的研究表明胶质细胞激活介导的神经炎症在神经退行性疾病发病中起着重要的作用。热休克蛋白70(heat shock protein 70,HSP70)是细...神经退行性疾病是由神经元进行性丢失而引起的神经系统功能障碍。尽管该类疾病的发病机制尚不清楚,但近期的研究表明胶质细胞激活介导的神经炎症在神经退行性疾病发病中起着重要的作用。热休克蛋白70(heat shock protein 70,HSP70)是细胞内重要的分子伴侣,对细胞内蛋白质进行质量调控。近年来研究表明HSP70也参与炎症的调控。中枢神经系统过表达HSP70可有效地抑制多种因素导致的胶质细胞激活引起的炎症反应、保护神经元和改善神经系统功能障碍。因此,研究HSP70对神经炎症的抑制作用对寻找有效的治疗神经退行性疾病的药物具有重要意义。本文主要综述HSP70对神经炎症的调节作用和以HSP70为靶点治疗神经退行性疾病的作用。展开更多
Objective To investigate the effects of Huaiqihuang Granules (槐杞黄颗粒, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropath...Objective To investigate the effects of Huaiqihuang Granules (槐杞黄颗粒, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms. Methods Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers. Results HQH ameliorated the rat’s general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis. Conclusion HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.展开更多
基金supported by the Young Scientists Foundation of Hubei Provincial Health Department,No.QJX2012-16
文摘Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.
文摘神经退行性疾病是由神经元进行性丢失而引起的神经系统功能障碍。尽管该类疾病的发病机制尚不清楚,但近期的研究表明胶质细胞激活介导的神经炎症在神经退行性疾病发病中起着重要的作用。热休克蛋白70(heat shock protein 70,HSP70)是细胞内重要的分子伴侣,对细胞内蛋白质进行质量调控。近年来研究表明HSP70也参与炎症的调控。中枢神经系统过表达HSP70可有效地抑制多种因素导致的胶质细胞激活引起的炎症反应、保护神经元和改善神经系统功能障碍。因此,研究HSP70对神经炎症的抑制作用对寻找有效的治疗神经退行性疾病的药物具有重要意义。本文主要综述HSP70对神经炎症的调节作用和以HSP70为靶点治疗神经退行性疾病的作用。
基金Supported by the National Natural Science Foundation of China(No.81373607)the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Science and Technology Funding for Life and Health Care of Jiangsu Province(No.BL2012032)
文摘Objective To investigate the effects of Huaiqihuang Granules (槐杞黄颗粒, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms. Methods Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers. Results HQH ameliorated the rat’s general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis. Conclusion HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.
文摘目的:探讨他克莫司联合雷公藤多苷对肾病综合征患者核转录因子kappa B(NF-κB)与炎症细胞因子(IL-1、TNF-α)的影响。方法 :选取我院肾病综合征患者129例,采用随机数字表法将其分为两组,对照组64例,采用他克莫司治疗;研究组65例,采用他克莫司联合雷公藤多苷治疗。采用Elisa方法检测血清NF-κB、IL-1、TNF-α水平,采用酶动力法测定血肌酐(Scr),采用尿素酶速率法测定血尿素氮(BUN),比较两组的临床疗效。结果 :研究组患者临床缓解率明显高于对照组(P<0.05)。治疗后,全部患者NF-κB、IL-1、TNF-α水平明显低于治疗前,治疗前后比较差异具有统计学意义(P<0.05),其中研究组NF-κB、IL-1、TNF-α水平明显低于对照组(P<0.05),治疗后,全部患者Scr、BUN、24 h Upro水平明显低于治疗前(P<0.05),其中研究组Scr、BUN、24 h Upro水平明显低于对照组(P<0.05)。两组患者药物不良反应率比较差异无统计学意义(P>0.05)。结论 :他克莫司联合雷公藤多苷显著降低肾病综合征患者NF-κB与IL-1、TNF-α炎症细胞因子,改善肾功能,且药物安全性较高。
