c-Jun氨基末端激酶信号通路及其抑制剂SP600125在大鼠杏仁核电刺激癫痫模型中的作用

目的 通过对杏仁核电刺激癫痫模型大鼠脑室内注射c-Jun氨基末端激酶(JNK)特异性抑制剂SP600125,观察海马区的病理变化和JNK水平的变化,探讨SP600125的作用.方法 将40只Wistar大鼠随机分为4组:空白组、点燃组、加药组和加药对照组各10只,10次癫痫发作后灌注取脑,Western blot法检测JNK的表达变化,进行尼氏和胶原纤维酸性蛋白(GFAP)染色,各组间进行比较.结果 Western blot显示点燃组海马区的JNK磷酸化水平(0.48±0.04)较空白组(0.38±0.04)和加药组(0.37±0.03)显著增高(P＜0.05),总JNK水平各组之间差异无统计学意义(P＞0.05).尼氏染色阳性细胞计数加药组(33.41±3.73)较加药对照组(20.10±5.11)显著增高(P＜0.05).点燃组GFAP阳性细胞计数(65.45±4.53)和加药对照组(67.18±3.52)较空白组(40.37±3.82)和加药组(43.51±1.83)显著增加(P＜0.05).结论 JNK信号通路可能参与颞叶癫痫海马硬化形成,表现为磷酸化JNK升高,SP600125通过抑制JNK可以缓解海马区病理变化.     

JNK抑制剂SP600125对脊髓损伤的影响

[目的]探讨JNK调控Notch信号通路抑制脊髓损伤的机制。[方法] 60只SD大鼠随机分为4组,其中,15只行椎板切除为假手术组,其余45只采用改良Allens法制作为急性脊髓损伤模型。干预组15只经腹腔注射含JNK抑制剂SP600125 4 mg/kg的溶液5μl;空白对照组15只不给予任何药物。安慰剂组15只经腹腔注射同等剂量(5μl)的生理盐水。假手术组不给予任何药物。观测动物残余尿量、排尿量。腹腔给药后48 h处死动物,取损伤段脊髓,检测JNK和Notch信号通路相关蛋白Notch1、Hes1的m RNA表达水平,用原位末端标记法(TUNEL)检测神经细胞凋亡情况。[结果]干预组和安慰剂组随时间推移排尿量减少,而残余尿量增加,不同时间点间差异均有统计学意义(P0.05)。RT-PCR检测结果显示,JNK mRNA表达水平由低至高依次为:干预组假手术组安慰剂组空白对照组,4组间差异具有统计学意义(P0.05);Notch1和Hes1的mRNA表达水平由低至高依次为:假手术组安慰剂组空白对照组干预组,4组间差异有统计学意义(P0.05);TUNEL检测细胞凋亡率干预组为(12.36±2.24)%,空白对照组为(25.93±3.31)%,安慰剂组为(26.12±2.45)%,假手术组为(1.32±0.52)%,4组间差异有统计学意义(P0.05)。[结论] JNK抑制剂SP600125可抑制JNK mRNA表达,减少大鼠脊髓损伤模型的神经细胞凋亡。     

MicroRNAs对骨质疏松症发病机制的研究进展

骨质疏松症是一种全身性骨代谢异常的疾病,发病的机制一直是研究热点、难点,目前主要集中在成骨细胞和破骨细胞方面,认为成骨细胞的功能下降和破骨细胞的活性增强是该病发生、发展的主要原因。miRNA是一种内源性高度保守的、单链的、非编码的小RNA,能够在基因转录后水平发挥负性调控作用。miRNA在骨质疏松症发病机制中的作用得到了广泛研究,不仅可调节成骨细胞的代谢,而且对破骨细胞的分化、增殖及凋亡等方面均起调控作用。本文梳理了最近miRNA在骨质疏松症中相关作用机制的文献,旨在为骨质疏松症的防治提供新思路。     

坏死性凋亡与骨质疏松症机制研究

骨质疏松症（ｏｓｔｅｏｐｏｒｏｓｉｓ,ＯＰ）是一种与增龄相关的全身代谢性骨骼疾病,典型特征为骨量减少伴骨组织微结构破坏, 使骨的脆性增加、易发生骨折等危险,对患者的生活质量产生严重的影响。坏死性凋亡（ｎｅｃｒｏｐｔｏｓｉｓ）是一种非半胱天冬酶 （ｃａｓｐａｓｅ）依赖性的程序性细胞死亡（ｐｒｏｇｒａｍｍｅｄ ｃｅｌｌ ｄｅａｔｈ,ＰＣＤ）形式,具有与坏死相似的形态学特征,其发生机制与受体相 互作用蛋白激酶１（ｒｅｃｅｐｔｏｒ?ｉｎｔｅｒａｃｔｉｎｇ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ １,ＲＩＰＫ１）、受体相互作用蛋白激酶３（ｒｅｃｅｐｔｏｒ?ｉｎｔｅｒａｃｔｉｎｇ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ ３, ＲＩＰＫ３）及下游的混合谱系激酶结构域样蛋白（ｍｉｘｅｄ ｌｉｎｅａｇｅ ｋｉｎａｓｅ ｄｏｍａｉｎ?ｌｉｋｅ ｐｒｏｔｅｉｎ,ＭＬＫＬ）的级联激活密切相关。随着对 ＯＰ 发病机制探索的不断深入,已有研究证实坏死性凋亡可通过影响成骨细胞、破骨细胞和骨细胞的活性和功能等生物学过 程,参与多种原因导致的ＯＰ 的发生和发展。本文着重阐述坏死性凋亡在ＯＰ 中的研究进展,旨在为防治ＯＰ 提供新的见解。     

Smad与骨质疏松症

骨质疏松症(osteoporosis,OP)是由成骨细胞(osteoblast,OB)负责的骨形成和破骨细胞(osteoclast,OC)负责的骨吸收之间的平衡被打破所致。已有大量研究证实转化生长因子-β(transforming growth factor-β,TGF-β)通路和骨形态发生蛋白(bone morphogenetic proteins,BMPs)通路能调控骨形成与骨吸收的平衡,而Smad蛋白家族(Smad)直接介导TGF-β通路和BMP通路下游的信号转导,在调节骨代谢过程中扮演重要的角色。本文针对OP,主要从Smad影响OB与OC的作用方面进行综述。     

益盖宁治疗骨质疏松症的疗效观察

目的：观察益盖宁对老年性和绝经后骨质疏松症患者的疗效。方法：48例患者益盖宁20Uim每周2次，加服碳酸钙每日750mg另48例患者单纯服用碳酸钙每日750mg作为对照。结果：益盖宁对患者疼痛和骨密度的改善作用优于对照组，能有效提高骨转换率，且益盖宁的副作用较轻。结论：益盖宁长期治疗可抑制骨吸收，提高骨密度，改善骨痛。     

糖皮质激素性骨质疏松症的发病机制

随着糖皮质激素（glucocorticoid,GC）的广泛使用,其所导致的糖皮质激素性骨质疏松症（glucocorticoid-induced osteoporosis,GIOP）越来越受到人们的关注。GC通过多种机制干扰骨质的形成和吸收,从而导致GIOP。本文从多方面对GIOP的病理机制进行综述,进一步探讨其发病机理。     

微RNAs在骨质疏松症发生发展中的作用及临床应用前景

骨质疏松症（OP）是一种常见的代谢性骨病,受遗传和环境因素影响,增加骨脆性和骨折的风险,从而严重影响患者的生活质量。越来越多的证据表明,遗传和环境因素通过表观遗传机制影响OP的发生发展。微RNAs(miRNAs)作为表观调控因子,能够调控成骨细胞和破骨细胞相关信号分子的表达,在骨代谢过程中发挥重要的调节作用。本文总结miRNAs调节成骨细胞和破骨细胞分化对OP的影响机制及miRNAs在临床应用中的探索,以期为开发OP诊疗的新方法提供一定的参考。     

左归丸对庆大霉素诱导的肾损伤大鼠MKK4、MKK7、JNK的影响

目的:探讨左归丸对庆大霉素诱导的肾损伤大鼠MKK4、MKK7、JNK的影响.方法:将40只雄性Wistar大鼠随机分为空白对照组、模型组、SP600125组、左归丸组,对照组给予腹腔注射0.9%生理盐水2.5 ml·kg-1·d-1,模型组腹腔注射硫酸庆大霉素100 ml·kg-1·d-1,SP600125组左侧腹腔注射硫酸庆大霉素100 ml·kg-1·d-1,2 h后右侧腹腔注射SP600125 15 ml·kg-1·d-1,左归丸组腹腔注射硫酸庆大霉素100 ml·kg-1·d-1和灌胃左归丸水溶液2 g·200 g-1·d-1,4组大鼠连续给药10 d.第11天测量各组大鼠尿NAG酶、血Scr、血BUN等生化指标;HE染色观察各种大鼠肾脏病理状况;以免疫组化技术检测各组大鼠肾脏MKK4、MKK7、JNK的表达,并采用Image pro-Plus6.0图像分析软件半定量分析;以Western blot方法检测各组大鼠肾脏MKK4、MKK7、JNK蛋白的表达.结果:生化指标结果显示:与对照组比较,模型组的大鼠尿NAG酶、血Scr、血BUN值显著升高,差异具有统计学意义(P<0.01);与模型组比较,SP600125组与左归丸组生化指标得到改善,差异具有统计学意义(P<0.05或P<0.01).免疫组化结果显示:与对照组比较,模型组MKK4、MKK7、JNK在肾小管大量表达,差异有统计学意义(P<0.01);与模型组比较,SP600125组与左归丸组表达少量,差异具有统计学意义(P<0.05或P<0.01).Western blot方法结果显示:模型组MKK4、MKK7、JNK蛋白灰度值较对照组明显升高(P<0.01),SP600125组与左归丸组较模型组灰度值下降(P<0.05).结论:左归丸对庆大霉素诱导肾损伤大鼠的保护作用可能与抑制MKK4、MKK7、JNK的表达有关.     

褪黑素防治骨质疏松症的研究现状

骨质疏松症是一种危害严重且发病率逐年增加的全身性代谢性骨病,是中老年的常见病、多发病。褪黑素是一种由松果体分泌的调节生物昼夜节律的信号分子。近年来国内外研究发现褪黑素具有促进成骨细胞增殖分化、抑制破骨细胞活性从而促进骨代谢平衡的作用。其中,褪黑素在多项骨质疏松症相关细胞实验、动物实验以及临床试验的骨代谢研究中均取得了良好的治疗效果。因其具有治疗骨质疏松症的潜在作用,笔者就其研究进展作一综述,并提出今后可能的研究方向和亟待解决的关键问题。     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

目的 观察鞘内注射c-Jun氨基末端蛋白激酶(c-Jun N-terminal protein kinase,JNK)特异性抑制剂SP600125对慢性压榨性损伤(chronic constriction injury,CCI)大鼠痛行为的影响.方法 雄性sD大鼠40只,随机分为5组(n=8). SP5组:CCI模型,鞘内注射SP600125 5μg;SP25组:CCI模型,鞘内注射SP600125 25 μg;SP50组:CCI模型,鞘内注射SP600125 50μg;DMSO组:CCI模型,鞘内注射2%二甲亚砜溶剂10 μl;Naive组:正常大鼠,鞘内注射SP600125 50μg.SP600125均溶于2%二甲亚砜10μl.CCI模型制作7 d后行鞘内注射,并测定大鼠机械缩足反射阈值(mechanical withdrawal threshold,MWT)及热缩足反射潜伏期(thermal withdrawal latency,TWL).结果 鞘内注射SP600125对正常大鼠的痛行为无影响.鞘内注射一定剂量SP600125能减轻CCI大鼠的机械痛敏及热痛敏.结论 鞘内注射一定剂量的SP600125能够减轻CCI大鼠的机械痛敏及热痛敏.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.     

鞘内注射JNK特异性抑制剂SP600125对CCI大鼠痛行为的影响

Objective To observe the effect of intrathecal administration of SP600125 on both MWT and TWL of rats after chronic constriction injury (CCI) of the sciatic nerve. Methods 40 male SD rats were randomized to deride into 5 groups (n=8). Rats in group SP5 received SP600125 5 μg after CCI; rats in group SP25 received SP600125 25 μg after CCI; rats in group SP50 received SP600125 50 μg after CCI; rats in group DMSO received 2% DMSO 10 μl after CCI; rats in group Naive received SP600125 50 μg without sciatic nerve injury. SP600125 was dissolved in 10 μl 2%DMSO solvent. On the 7th day after CCI, MWT and TWL were determined with yon Frey filaments and thermal radiation apparatus repectively after intrathecal administration of SP600125. Results Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI rather than normal rats. Conclusion Intrathecal administration certain dosage of SP600125 could attenuate the established mechanical allodynia and thermal hyperalgesia induced by CCI.