Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson's disease in rats

The present study was undertaken to investigate the neuroprotective effects of resveratrol on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease in rats. 6-OHDA-induced Parkinson's disease rat model involves chronic inflammation, mitochondrial dysfunction, and oxidative stress, and the loss of the dopaminergic neurons in the substantia nigra is the predominant lesion. Resveratrol has been shown to have anti-inflammatory actions, and thus was tested for its beneficial effects using 6-OHDA-induced Parkinson's disease rat model. Adult Sprague–Dawley (SD) rats were unilaterally injected with 6-OHDA (5 µg/2 µl) into the right striatum, and the striatum damage was assessed by rotational test, ultrahistopathology, and molecular alterations. Resveratrol (10, 20 and 40 mg/kg) was then given orally to Parkinson's disease rats, daily for 10 weeks to examine the protective effects. Rotational test (turns of rats) showed that resveratrol significantly attenuated apomorphine-induced turns of rats in 6-OHDA-injuried Parkinson's disease rat model as early as two weeks of administration. Ultrastructural analysis showed that resveratrol alleviated 6-OHDA-induced chromatin condensation, mitochondrial tumefaction and vacuolization of dopaminergic neurons in rat substantia nigra. Furthermore, resveratrol treatment also significantly decreased the levels of COX-2 and TNF-α mRNA in the substantia nigra as detected by real-time RT-PCR. COX-2 protein expression in the substantia nigra was also decreased as evidenced by Western blotting. These results demonstrate that resveratrol exerts a neuroprotective effect on 6-OHDA-induced Parkinson's disease rat model, and this protection is related to the reduced inflammatory reaction.     

众生丸对H1N1流感小鼠的保护及免疫调节作用研究

目的研究众生丸对H1N1流感病毒感染小鼠的保护及免疫调节作用。方法以奥司他韦为阳性药,H1N1流感病毒滴鼻感染小鼠复制小鼠病毒性肺炎模型。比较小鼠病毒性肺炎模型的肺指数、肺组织形态学、死亡保护率、小鼠T淋巴细胞亚群和细胞因子干扰素-γ(Interferon-γ,IFN-γ)、白细胞介素-10(interleukin-10,IL-10)的数量变化。结果与病毒对照组比较,众生丸可显著降低H1N1感染小鼠的肺指数,提高存活率,调节T细胞亚群含量,促进血清中IFN-γ和IL-10产生。结论众生丸可通过减轻炎症,调节免疫而减轻H1N1亚型流感病毒所致小鼠肺部病变,提高染毒小鼠存活率。     

通络救脑口服液对实验性类AD大鼠血清细胞因子含量的影响

目的探讨大鼠大脑海马立体定向注射β-淀粉样蛋白1-40对血清TNF-α和IL-1β含量的影响及通络救脑口服液对其干预作用。方法140只Sprague-Dawley(SD)大鼠随机分为空白对照组、假手术组、阴性对照组、阳性对照组、实验组(12,24,48 mg.kg-1.d-1)共7组。采用大脑海马立体定向注射β-淀粉样蛋白1-40诱导Alzheimer's病动物模型后,药物干预4周,第5周应用双抗夹心酶联免疫吸附测定检测TNF-α和IL-1β含量。结果模型组TNF-α,IL-1β含量分别为(120.97±7.32)和(88.54±4.07),TNF-α和IL-1β含量显著多于假手术组(TNF-α为85.43±6.55,IL-1β为68.29±4.37,P<0.01),表明模型组TNF-α和IL-1β含量升高;与模型组比较,盐酸多萘哌齐组(TNF-α为106.86±7.09;IL-1β为1.80±0.23)、通络救脑口服液12,24,48 mg.kg-1.d-1剂量组(TNF-α分别为100.08±9.29、99.97±6.09和85.90±4.40;IL-1β分别为(77.56±6.97),(77.85±3.81)和(67.87±2.38)TNF-α和IL-1β含量升高显著减少。结论大鼠海马注射β-淀粉样蛋白1~40后大鼠血清TNF-α和IL-1β含量明显增高,通络救脑口服液可以降低血清TNF-α和IL-1β的含量,从而发挥其抗老年性痴呆的作用。     

茵栀黄颗粒联合蓝光治疗黄疸疗效及对新生儿肝功能、胆红素、脑功能的影响

目的:研究茵栀黄颗粒口服联合蓝光治疗对新生儿黄疸肝功能、胆红素水平及脑功能的影响。方法:选择120例新生儿黄疸患儿并随机分为观察组和对照组各60例。对照组患儿采用蓝光治疗; 观察组患者在对照组基础上联合茵栀黄颗粒治疗,两组均治疗7 d。比较两组患儿治疗前后肝功能、胆红素水平、炎症反应水平及治疗后脑功能损伤情况和疗效。结果:治疗后观察组谷草转氨酶(AST)和谷丙转氨酶(ALT)水平显著低于对照组(P<0.05); 总胆红素(TBIL)、间接胆红素(IBIL)水平显著低于对照组(P<0.05); 白介素-6(IL-6)、C反应蛋白(CRP)水平显著低于对照组(P<0.05); 脑功能正常率显著高于对照组(P<0.05); 总有效率明显高于对照组(P<0.05)。结论:新生儿黄疸患儿通过茵栀黄颗粒口服联合蓝光治疗对改善肝功能、调节胆红素水平和炎症反应、改善脑功能有积极意义,整体疗效较理想。     

Inhibitory effects of casticin on migration of eosinophil and expression of chemokines and adhesion molecules in A549 lung epithelial cells via NF-κB inactivation

Ethnopharmacological relevance

The fruits of Vitex rotundifolia L. have long been used for the treatment of inflammation of the respiratory tract in East Asia.

Aim

To determine if casticin, one of the constituents of Vitex rotundifolia L., has anti-allergic and anti-inflammatory effects in asthma.

Materials and methods

The in vitro anti-inflammatory activity of casticin was studied in A549 human type II-like epithelial lung cells using an eotaxin inhibition assay. Additionally, its effects on eotaxin, regulated on activation normal T cell expressed and secreted (RANTES), vascular cell adhesion molecule (VCAM)-1, and inter-cellular adhesion molecule (ICAM)-1 expression were investigated by real time-polymerase chain reaction (real time-PCR). The inhibition of nuclear factor κB (NF-κB) activity in the presence of casticin was determined by analyzing confocal microscopy images of fluorescence immunocytochemical analysis while the suppression of inhibitory κB (IκB)-α phosphorylation was studied using Western blot analysis. Finally, the inhibitory effect of casticin on eosinophil migration toward prestimulated A549 cell media was measured using the human eosinophilic leukemia cell line.

Results and discussion

Casticin significantly suppressed eotaxin production in cytokine activated A549 lung epithelial cells. Casticin also suppressed the mRNA expression levels of eotaxin, RANTES, VCAM-1, and ICAM-1, which subsequently contributed to the inhibition of eosinophil migration. Furthermore, casticin inhibited IκB-α phosphorylation and nuclear translocation of p65 in A549 cells.

Conclusion

Casiticin inhibited the eosinophil migration and activity of chemokines and adhesion molecules involved in the inflammatory process of asthma by suppressing the NF-κB pathway. These results suggest that casticin has the potential for use in the treatment of allergic asthma.     

EGCG调控miR-133a/b-3p和TGF-β1/Smad3抗慢性阻塞性肺疾病的作用研究

目的:探讨表没食子儿茶素没食子酸酯(EGCG)对慢性阻塞性肺疾病(COPD)大鼠的保护作用和机制。方法:通过烟熏和脂多糖滴注建立大鼠COPD模型。每日灌胃给予100或200 mg/kg EGCG,4 w后观察肺部形态学改变。检测肺促炎细胞因子、MDA、GSH、SOD水平。免疫组化法评价纤维连接蛋白(fibronectin)和波形蛋白(vimentin)表达情况,Western blot检测TGF-β_1、p-Smad3表达水平,q PCR检测fibronectin、vimentin、TGF-β_1mRNA和微小RNA(miR)-133a/b-3p水平。结果:与正常对照组比较,模型组肺泡壁破损明显,肺组织促炎细胞因子、MDA及Smad3磷酸化水平显著升高,GSH、SOD、miR-133a/b-3p水平显著降低,fibronectin、vimentin、TGF-β_1蛋白表达显著升高。与模型组比较,EGCG能改善COPD大鼠的肺损伤,显著降低促炎细胞因子、MDA和Smad3的磷酸化水平,升高GSH、SOD、miR-133a/b-3p水平,并减少fibronectin、vimentin、TGF-β_1蛋白表达。结论:EGCG能改善COPD大鼠的肺损伤,其作用机制与调控肺TGF-β_1/Smad3和miR-133a/b-3p水平,抑制氧化应激和炎症有关。     

中医药通过肺淋巴管系统干预间质性肺疾病的研究进展

间质性肺疾病(ILD)是一种以弥漫性肺实质的炎症和肺纤维化改变为特征的疾病。淋巴管系统在炎症和纤维化疾病中发挥重要作用。已知在炎症性疾病和纤维化疾病中淋巴管系统具有重要功能。但在间质性肺疾病中淋巴管系统作用的相关研究较少,随着科技的进步,逐渐发现了间质性肺疾病中肺淋巴管系统发挥作用的重要机制。且近年来运用中药疗法干预淋巴管系统来治疗疾病成为研究热点。现将基于肺淋巴管系统与间质性肺疾病中的相关性来探讨中医药对间质性肺疾病的干预作用。     

水飞蓟宾对硫代乙酰胺所致肝损伤状态下CYP3A的调节作用及机制

目的：水飞蓟宾（sB）是植物奶蓟的主要成分,长期以来被用于治疗各种肝脏疾病。由于肝病往往伴随有CYP450酶的功能失调,因此本文以硫代乙酰胺（TAA）引起的大鼠肝损伤为模型,研究水飞蓟宾的肝保护作用和对CYP3A的调控作用之间的关系。方法：血清生化指标检测和肝脏病理切片实验评价水飞蓟宾的保肝作用。免疫组化实验测定0【一SMA的表达,ELISA试剂盒测定大鼠肝脏炎症因子的表达。实时定量PCR和westernblot实验考察CYP3A和PXR的mRNA和蛋白表达水平变化,咪达唑仑4一羟基化反应测定CYP3A的活性。siRNA转染实验沉默PXR后考察PXR在硫代乙酰胺细胞毒和CYP3A调节中的作用。结果：水飞蓟宾表现出明显的保肝、抗炎、抗纤维化作用,并能有效逆转硫代乙酰胺导致的大鼠肝脏CYP3A和PXR表达减少以及PXR的入核减少。PXR沉默实验显示PXR参与了水飞蓟宾的细胞保护和CYP3A调控过程。结论：PXR是参与CYP3A调控的重要因子,很可能是水飞蓟宾在硫代乙酰胺导致的大鼠肝损伤模型中的作用靶点,同时也提示在治疗肝脏疾病时要注意与水飞蓟宾合用的药物可能与水飞蓟宾之间存在潜在的药物相互作用。     

急进高原个体机体炎性改变及其胃肠黏膜屏障损伤情况分析

目的:探讨急进高原个体机体炎性改变及其胃肠黏膜屏障损伤的特点。方法:对20例由平原急进高原个体于进入高原前、进入高原第三天和第七天进行胃镜检查,并对进入高原后消化系统的症状发生情况进行调查,同步抽取血液标本,做血常规的白细胞总数(WBC)、中性粒细胞(N)、淋巴细胞(L)及白介素-1(IL-1)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血小板活化因子(PAF)等炎症介子的含量进行检测。结果:20例平原个体急进高原后血常规WBC、N及IL-1、IL-6、TNF-α、PAF等炎症介子均较平原显著升高,L较平原显著降低,均以进入高原第三天改变最为显著,与进入前比较P<0.01,与第七天比较P<0.05,L为第三天与进入前比较P<0.05、与第七天比较P>0.05。胃镜检查者,进入高原第三天及第七天胃镜检查阳性例数分别为17例(约85%)和10例(50%),与进入高原前比较差异均具有显著性(P<0.01),胃镜下主要表现有胃黏膜出血、充血、淤血、糜烂、溃疡及胆汁反流等,13例存在不同程度的消化系统症状(占65%)。结论:高原缺氧对急进高原个体肠道黏膜屏障存在明显的损伤,并引发机体的炎性改变。而机体的这种炎性改变又可能进一步加重胃肠道的黏膜屏障损伤。     

Atractylodin attenuates lipopolysaccharide-induced acute lung injury by inhibiting NLRP3 inflammasome and TLR4 pathways

Acute lung injury (ALI) arises from uncontrolled pulmonary inflammation with high mortality rates. Atractylodin (Atr) is a polyethylene alkynes and has been reported to possess anti-inflammation effect. Thus, we aimed to investigate the protective effect of Atr on lipopolysaccharide (LPS)-induced inflammatory responses ALI. The results indicated that Atr treatment not only significantly attenuated LPS-stimulated histopathological changes but also lessened the myeloperoxidase (MPO) activity, the wet-to-dry weight ratio of the lungs, protein leakage and infiltration of inflammatory cells. Moreover, Atr inhibited the tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and monocyte chemoattractant protein (MCP)-1 secretion in BALF. Further study demonstrated that such inhibitory effects of Atr were due to suppression of nucleotide-binding domain-(NOD-) like receptor protein 3 (NLRP3) inflammasome and toll like receptor 4 (TLR4) activation, likely contributing to its anti-inflammatory effects. Collectively, these findings suggest that Atr may be an effective candidate for alleviating LPS-induced inflammatory responses.