双黄连对动脉粥样硬化大鼠TLR4/MyD88/NF-κB信号通路表达的影响实验研究

目的探究双黄连对动脉粥样硬化大鼠体内TLR4/MyD88/NF-κB信号通路表达的影响。方法建立动脉粥样硬化大鼠模型,进行双黄连不同剂量的处理后,对大鼠进行相关检测。结果双黄连处理组大鼠血清中的总胆固醇、甘油三酯、高密度脂蛋白和低密度脂蛋白均明显低于模型组,高剂量组效果更明显;将胸主动脉进行HE染色后发现,相比模型组,双黄连处理组均有管腔狭窄的减轻,脂质斑块的减少,泡沫细胞沉积的减少,蓝色颗粒钙化病灶的缩小;免疫组化实验和Western Blot实验检测发现,双黄连处理组大鼠的动脉组织中TLR4、MyD88、NF-κB表达相比模型组发生了明显降低,且高剂量组降低更明显。结论双黄连有利于减轻大鼠动脉粥样硬化的病症,其机理在于降低TLR4、MyD88、NF-κB蛋白的表达水平,且疗效显著。     

三七对酒精性肝病大鼠肝组织NF-κB、c-Jun表达的影响

 目的 观察三七对酒精性肝病大鼠肝组织NF-κB、c-Jun表达的影响。方法 SD雄性大鼠连续14周给予酒精建立酒精性肝病模型,随机分为模型对照组,三七高、低剂量组和硫普罗宁组,在模型制备同时,每天下午分别灌服给药,连续14周。同时设立正常对照组,连续14周灌胃给水。免疫组化法检测肝组织中NF-κBp65/IκBα、p-IκBα、p-JNK、c-Jun蛋白的表达。结果 模型对照组大鼠肝组织NF-κBp65/IκBα、p-IκBα、p-JNK/c-Jun均较正常对照组明显升高（P<0.01）;三七高、低剂量组大鼠肝组织NF-κBp65/IκBα、p-IκBα、p-JNK/c-Jun表达较模型对照组明显降低（P<0.01,P<0.05）。结论 三七能显著抑制肝组织中NF-κBp65/IκBα、p-JNK/c-Jun的过度表达,这可能是其有效防治酒精性肝病发生发展的重要机制之一。     

针刺对脑缺血再灌注大鼠海马组织核转录因子-κB表达及含量的影响

目的:观察电针对脑缺血再灌注大鼠核转录因子-κB(NF-κB)信号分子表达和含量的影响,探讨针刺抗局灶性脑缺血再灌注损伤的神经细胞信号转导机制。方法:将120只SD大鼠随机分为正常组、假手术组、模型24h组、模型48h组、模型72h组、电针治疗24h组、电针治疗48h组、电针治疗72h组。采用改良线栓法制备局灶性脑缺血(MCAO)再灌模型,电针“大椎”、双侧“内关”穴(连续波,频率120次/min,强度1mA,持续30min)。运用免疫组化检测法和蛋白免疫印迹法,检测海马组织NF-κB-p65核转录因子蛋白的表达与含量。结果:模型各组大鼠缺血侧海马CA1区NF-κB-p65蛋白表达显著高于正常组和假手术组(P<0·05),也显著高于电针治疗同时相各组(P<0·01),NF-κB移位于核明显;模型各组大鼠缺血侧海马组织NF-κB-p65蛋白含量比电针治疗同时相各组高,有显著性差异(P<0·05)。结论:电针能下调脑缺血再灌注海马组织NF-κB蛋白水平,阻滞其转位于核,发挥神经保护作用。     

三妙丸类方及川牛膝对急性痛风性关节炎大鼠炎症反应的作用机制研究

目的：从NF-κB信号传导通路角度探讨三妙丸类方及引经药川牛膝对急性痛风性关节炎大鼠炎症反应的作用及机制。方法：70只大鼠随机取10只作为正常组,其余60只大鼠制备急性痛风性关节炎大鼠模型,随机分为模型组、二妙丸组、三妙丸低剂量组、三妙丸高剂量组、川牛膝低剂量组、川牛膝高剂量组。观察各组大鼠踝关节周径的变化;药物干预3天后,取大鼠滑膜组织,运用ELISA法、Westernblot法测定细胞因子水平及NF-κBP65蛋白表达水平;对滑膜组织进行HE染色,观察其病理学变化。结果：各药物干预组大鼠滑膜组织NF-κBP65、TNF-α、IL-6、IL-8、滑膜组织病理学积分低于模型组（P〈0.01,P〈0.05）。结论：三妙丸类方及川牛膝通过下调NF-κBP65蛋白表达,抑制TNF-α、IL-6、IL-8的水平,减轻急性痛风性关节炎大鼠踝关节的炎症反应,以三妙丸高剂量组疗效尤为显著;三妙丸抗炎作用优于二妙丸,机制在于引经药川牛膝对二妙丸的药效协同作用。     

尿毒清颗粒治疗糖尿病肾病相关机理研究进展

尿毒清颗粒已在临床中应用数十年,其通过对TGF-β1、nephrin、podocin蛋白、Cys C、NF-κB及VEGF的表达进行拮抗性干预,改善高糖、高脂、微炎症等危险状态,以保护肾小球内皮细胞、足细胞,防止肾小球硬化和间质纤维化,稳定肾功能,修复肾脏病理改变,减缓DN进展,其保护肾脏的作用机理非常明确,该药价格适中,并且适用于任何原因引起的慢性肾功能衰竭,长期服用较为安全。     

Evidence of anti-inflammatory effects of Passiflora edulis in an inflammation model

The popular medicine Passiflora edulis has been used as a sedative, tranquilizer, against cutaneous inflammatory diseases and intermittent fever. Most of the pharmacological investigations of Passiflora edulis have been addressed to its Central Nervous System activities, such as anxiolytic, anticonvulsant and sedative actions. Otherwise, there are few reports about the anti-inflammatory activity of the Passiflora species. The aim of this study was to investigate the mechanism of the anti-inflammatory effect of aqueous lyophilized extract obtained from leaves of Passiflora edulis var. flavicarpa Degener (Passifloraceae) in the mouse model of pleurisy induced by carrageenan (Cg), bradykinin, histamine or substance P, observing the effects upon leucocytes migration, myeloperoxidase (MPO), nitric oxide (NO) concentrations and tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1beta) levels. RESULTS: Passiflora edulis (250mg/kg) administered by intraperitoneal route (i.p.) inhibited the leukocyte, neutrophils, myeloperoxidase, nitric oxide, TNFalpha and IL-1beta levels (P<0.01) in the pleurisy induced by carrageenan. Passiflora edulis (250-500mg/kg, i.p.) also inhibited total and differential leukocytes in the pleurisy induced by bradykinin, histamine or substance P (P<0.05). CONCLUSION: Several mechanisms, including the inhibition of pro-inflammatory cytokines (TNFalpha, IL-1beta), enzyme (myeloperoxidase) and mediators (bradykinin, histamine, substance P, nitric oxide) release and/or action, appear to account for Passiflora edulis's actions.     

Attenuation of diabetic nephropathy by Chaihuang-Yishen granule through anti-inflammatory mechanism in streptozotocin-induced rat model of diabetics

Ethnopharmacological relevance

Traditional Chinese medical herbs have been used in China for a long time to treat different diseases. Based on traditional Chinese medicine (TCM) principle, Chaihuang-Yishen granule (CHYS) was developed and has been employed clinically to treat chronic kidney disease including diabetic nephropathy (DN). The present study was designed to investigate its mechanism of action in treatment of DN.

Materials and methods

Diabetic rats were established by having a right uninephrectomy plus a single intraperitoneal injection of STZ. Rats were divided into four groups of sham, diabetes, diabetes with CHYS and diabetes with fosinopril. CHYS and fosinopril were given to rats by gavage for 20 weeks. Samples from blood, urine and kidney were collected for biochemical, histological, immunohistochemical and molecular analyses.

Results

Rats treated with CHYS showed reduced 24 h urinary protein excretion, decreased serum TC and TG levels, but CHYS treatment did not affect blood glucose level. Glomerular mesangial expansion and tubulointerstitial fibrosis in diabetic rats were significantly alleviated by CHYS treatment. Moreover, CHYS administration markedly reduced mRNA levels of NF-κB p65 and TGF-β1, as well as decreased protein levels of NF-κB p65, MCP-1, TNF-α and TGF-β1 in the kidney of diabetic rats.

Conclusions

CHYS ameliorates renal injury in diabetic rats through reduction of inflammatory cytokines and their intracellular signaling.     

导痰汤通过NF-κB信号通路抑制人脐静脉内皮细胞ICAM-1表达的研究

目的:研究导痰汤能否通过对核因子-κB(NF-κB)信号通路的调节而干预ICAM-1的表达,以揭示导痰汤治疗动脉粥样硬化的机制。方法:通过PCR和Western blot等方法,观察导痰汤对肿瘤坏因子-α(TNF-α)刺激脐静脉内皮细胞(HUVEC)培养内皮细胞细胞间黏附分子-1(ICAM-1)和NF-κB表达的影响。结果:TNF-α诱导组ICAM-1和NF-κB显著高于空白对照组和导痰汤对照组(P<0.01);使用导痰汤含药血清或吡咯烷二硫氧基甲酸(PDTC)处理后,ICAM-1和NF-κB p65表达显著下降(P<0.05,P<0.01);NF-κB活性与ICAM-1 mRNA水平呈显著正相关(r=0.716,P<0.01)。结论:导痰汤可以调节NF-κB信号通路,从而有效抑制TNF-α刺激所致的脐静脉内皮细胞ICAM-1的表达。     

锌指蛋白A20对树突状细胞的免疫调控及其在炎症性肠病发病机制中的作用

泛素化修饰对蛋白质降解及多种细胞功能都具有重要的调控作用,如DNA损伤修复、细胞周期调控、细胞生长、免疫系统功能等。泛素修饰酶锌指蛋白A20被认为是调控机体免疫和炎症反应的重要门户,为NF-κB信号通路中的关键负性调控因子。树突状细胞(DC)是专职的抗原提呈细胞,可以通过多种受体识别炎性反应或病原微生物,是维持机体免疫稳态的关键调节者。近年来,有研究表明,A20在DC功能的调控中发挥着重要作用,可能参与了炎症性肠病的发生和发展。文章基于最新的研究进展,总结A20对DC的免疫调控及其在炎症性肠病发病机制中的作用。     

Inhibition of homodimerization of Toll-like receptor 4 by curcumin

Toll-like receptors play a key role in sensing microbial components and inducing innate immune responses. Ligand-induced dimerization of TLR4 is required for the activation of downstream signaling pathways. Thus, the receptor dimerization may be one of the first lines of regulation in activating TLR-mediated signaling pathways and induction of subsequent immune responses. LPS induces the activation of NF-kappaB and IRF3 through MyD88- or TRIF-dependent pathways. Curcumin, a polyphenol found in the plant Curcuma longa, has been shown to suppress the activation of NF-kappaB induced by various pro-inflammatory stimuli by inhibiting IKKbeta kinase activity in MyD88-dependent pathway. Curcumin also inhibited LPS-induced IRF3 activation. These results imply that curcumin inhibits both MyD88- and TRIF-dependent pathways in LPS-induced TLR4 signaling. However, in TRIF-dependent pathway, curcumin did not inhibit IRF3 activation induced by overexpression of TRIF in 293T cells. These results suggest that TLR4 receptor complex is the molecular target of curcumin in addition to IKKbeta. Here, we report biochemical evidence that phytochemicals (curcumin and sesquiterpene lactone) inhibit both ligand-induced and ligand-independent dimerization of TLR4. Furthermore, these results demonstrate that small molecules with non-microbial origin can directly inhibit TLRs-mediated signaling pathways at the receptor level. These results imply that the activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain dietary phytochemicals we consume daily.