喜炎平注射液对LPS致急性肺损伤大鼠肺泡灌洗液中细胞因子含量的影响

目的:通过观察喜炎平注射液对LPS致急性肺损伤大鼠肺泡灌洗液(BALF)中细胞因子含量的影响,以探讨其治疗急性肺损伤的作用机制。方法:尾静脉注射LPS(2mg/kg)建立大鼠ALI模型,采用ELISA法检测造模后2h、4h、6h后大鼠BALF中TNF-α、IL-1β、IL-8、IL-4、IL-6和IL-10的含量,考察喜炎平注射液的影响。结果:LPS诱发ALI过程中,大鼠BALF中TNF-α、IL-1β、IL-6、IL-8、IL-4、IL-10含量均明显升高,TNF-α、IL-1β、IL-4及IL-10含量在LPS注射2h时均显著高于正常组(P<0.05),IL-6、IL-8含量在LPS注射2h时均显著高于正常组(P<0.05),给予喜炎平注射液后各时间点上述变化均得到一定改善。结论:喜炎平注射液可能通过抑制促炎因子的释放而发挥抗炎作用。     

Garcinia buchananii bark extract is an effective anti-diarrheal remedy for lactose-induced diarrhea

Ethnopharmacological relevance: The extract from the stem bark of Garcinia buchananii trees is used as an anti-diarrhea remedy in sub-Saharan Africa. We tested the hypothesis that G. buchananii bark extract and its anti-motility fractions are effective treatments against lactose-induced diarrhea.     

槐定碱与TLR4/MD-2阻断剂对LPS诱导的RAW264.7巨噬细胞TLR4-NF-κB-TNF-α通路的影响

目的:研究槐定碱及TLR4/MD-2阻断剂对LPS诱导的RAW264.7巨噬细胞TLR4-NF-κB-TNF-α通路的影响,探讨其抗内毒素的药理机制。方法:培养RAW264.7巨噬细胞,分为5组:空白对照组,LPS模型组,槐定碱+LPS组,TLR4/MD-2阻断剂+LPS组,TLR4/MD-2阻断剂+槐定碱+LPS组,各组分别于处理完毕后120 min时收集细胞及细胞培养液。West-ern blot检测TLR4蛋白表达,免疫细胞化学检测NF-κB蛋白的分布与表达,逆转录聚合酶链反应(RT-PCR)检测NF-κB,TNF-αmRNA表达,放射免疫分析法检测细胞培养液中TNF-α含量。结果:与LPS模型组比较,槐定碱+LPS组TLR4蛋白,NF-κBmRNA与NF-κB入核率,TNF-αmRNA及培养液中TNF-α含量均显著降低(P<0.01);TLR4/MD-2阻断剂+LPS组与TLR4/MD-2阻断剂+槐定碱+LPS组NF-κB mRNA及NF-κB入核率,TNF-αmRNA及培养液中TNF-α含量均低于LPS模型组(P<0.01),接近空白对照组,但2组之间上述各值的差异均无统计学意义。结论:TLR4/MD-2可能是槐定碱作用的靶位之一,槐定碱抑制TLR4-NF-κB-TNF-α通路活化可能是其抗内毒素机制之一。     

Immuno-enhancement effects of Shenqi Fuzheng Injection on cyclophosphamide-induced immunosuppression in Balb/c mice

Ethnopharmacological relevance

Radix Codonopsis and Radix Astragali, of which Shenqi Fuzheng Injection (SFI) is composed, are commonly used in traditional Chinese medicine to improve immune function against chronic diseases.

Aim of the study

The present study was thus designed to systematically elucidate the in vivo immuno-enhancement effects of SFI in immunosuppressed mice induced by cyclophosphamide (Cy) treatment.

Materials and methods

Balb/c mice were injected intraperitoneally (i.p.) once daily with low-dose (2.5 g raw materials/kg), intermediate-dose (5 g raw materials/kg), high-dose (10 g raw materials/kg) of SFI for 10 consecutive days, respectively, accompanied by i.p. injection of Cy (80 mg/kg) on Days 4-6.

Results

Compared with vehicle group, low-, intermediate- and high-dose SFI treatment accelerated recovery dose-dependently of spleen index, peripheral white blood cell and bone marrow cell counts, enhanced T cell and B cell proliferation responses, as well as splenic nature killer cell activity and peritoneal macrophage phagocytosis, and restored the level of interleukin-2 in the serum. Furthermore, SFI treatment promoted recovery of the amount of peripheral white blood cells on Day 6, rather than recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF) did.

Conclusions

These results demonstrate, for the first time, that chronic treatment with SFI results in accelerating recovery of immunosuppression in Cy-treated mice, which is competent in taking into consideration for both precautions and remedy. Our findings provide experimental evidences for further researches and clinical application in cancer patients undergoing chemotherapy.     

姜黄素通过抑制PI3K/Akt信号通路改善LPS诱导的视网膜炎症

目的:本研究旨在调查姜黄素是否能减轻动物模型和人视网膜色素上皮细胞(ARPE)-19细胞的视网膜炎症。方法:在体内,雄性C57/B6小鼠腹腔注射姜黄素3d,然后腹腔注射脂多糖(LPS;10mg/kg)诱导视网膜炎症。LPS作用24h后,通过RT-PCR检测促炎细胞因子的mRNA水平。伴刀豆球蛋白凝集素灌注标记技术评估了白细胞对视网膜脉管系统的粘附。用蛋白质定量试剂盒测量前房中的蛋白浓度。在体外,培养ARPE-19细胞。用细胞计数试剂盒8(CCK-8)法测量来选择姜黄素的最佳作用浓度。在用5μg/mL LPS刺激之前,将ARPE-19细胞在有或没有姜黄素的情况下孵育1h。通过RT-PCR和ELISA测量促炎细胞因子。通过蛋白质印迹分析PI3K/Akt表达。结果:姜黄素预处理可显著抑制EIU相关白细胞粘附于视网膜血管和前房蛋白渗漏。体内应用姜黄素后,炎症细胞因子(如IL-1β,IL-6和TNF-α)的mRNA表达水平也显著降低。同时,姜黄素在ARPE-19细胞的mRNA和蛋白质水平上均显著减弱IL-6,IL-8和MCP-1的表达。姜黄素抑制LPS激活的ARPE-19细胞中的PI3K/Akt磷酸化以及NF-κB激活。结论:姜黄素对LPS诱导的视网膜炎症具有预防作用,其作用似乎与PI3k/Akt信号传导途径的抑制有关。     

Neurotropin inhibits neuroinflammation via suppressing NF-κB and MAPKs signaling pathways in lipopolysaccharide-stimulated BV2 cells

Neurotropin (NTP) is a widely used drug in China and Japan mainly for the treatment of chronic pain and peripheral inflammation. Nevertheless, the effects of NTP on neuroinflammation have not been explored. In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively. Western blotting was conducted to measure the protein levels of major genes in MAPKs and NF-κB signaling pathways. Results demonstrated that NTP could attenuate the production of pro-inflammatory cytokines. Furthermore, NTP inhibited the activation of NF-κB signaling by decreasing the translocation of NF-κB p65 to the nucleus and suppressed the MAPKs signaling pathway via inhibition of the phosphorylation of p38, ERK and JNK. Taken together, these findings suggest that neurotropin exerts anti-inflammatory effects by suppressing the production of pro-inflammatory mediators via inhibition of NF-κB and MAPKs signaling pathways in LPS-stimulated BV-2 cells.     

Reduced tubular degradation of glomerular filtered plasma albumin is a common feature in acute and chronic kidney disease

Tubular epithelial cells take up and degrade plasma albumin filtered by the glomerulus. Tubular damage resulting in reduced albumin uptake or degradation has been suggested as one mechanism contributing to albuminuria in kidney disease. This study investigated whether tubular albumin uptake or degradation is altered in acute and chronic glomerular disease. Mouse models of acute glomerular injury (anti‐GBM disease and LPS‐induced albuminuria) and chronic disease (streptozotocin‐induced diabetes and db/db mice) were examined. Mice were injected intravenously with Alexa‐albumin plus DQ‐albumin and killed 20 minutes later. Tubular uptake of albumin (Alexa‐albumin) and albumin degradation (Dye Quenched (DQ)‐albumin) was assessed in tissue sections via confocal microscopy. Tubular uptake of Alexa‐albumin in the models of diabetic nephropathy was not different to normal mice. However, the fluorescence signal resulting from degradation of DQ‐albumin was significantly reduced in db/db mice, and the ratio of degraded to intact albumin was reduced in both models. The ratio of degraded to intact albumin in tubules was also reduced in the anti‐GBM model. In the LPS model, both tubular uptake and degradation of albumin were significantly reduced, with a substantial reduction in the ratio of degraded to intact albumin in tubules. LPS stimulation of cultured tubular epithelial cells inhibited albumin uptake, indicating a direct role for LPS in modifying tubular handling of albumin. In conclusion, reduced degradation of filtered albumin in the proximal tubule is a common feature of glomerular diseases. This may be a general mechanism whereby tubular dysfunction contributes to the development of albuminuria.     

生长抑素联合乌司他丁治疗粘连性肠梗阻的临床研究

目的探讨注射用生长抑素联合注射用乌司他丁治疗粘连性肠梗阻的临床疗效。方法选取2012年2月—2017年2月北京市顺义区医院和河北省第七人民医院收治的76例粘连性肠梗阻患者作为研究对象,将患者随机分为对照组和治疗组,每组38例。对照组静脉滴注注射用乌司他丁,将10万单位乌司他丁溶于0.9%氯化钠溶液250 mL中,1次/d。治疗组在对照组治疗的基础上静脉滴注注射用生长抑素,0.25mg/h,直到肛门恢复排便、排气。观察两组患者的临床疗效,比较两组的临床指标、血清炎性因子水平和不良反应情况。结果治疗后,治疗组的总有效率为84.21%,显著高于对照组的68.42%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组胃肠减压量、腹胀缓解时间和排气恢复时间明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清内毒素(LPS)、超敏C反应蛋白(hs-CRP)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组血清炎性因子水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗期间,治疗组不良反应总发生率为7.89%,低于对照组的26.32%,两组不良反应发生率比较差异具有统计学意义(P0.05)。结论注射用生长抑素联合注射用乌司他丁治疗粘连性肠梗阻的具有较好的临床疗效,可显著降低患者炎症反应,不良反应低,具有一定的临床推广应用价值。     

LPS诱导HUVEC凋亡的分子机制

目的:从脂多糖(LPS)所致血管内皮细胞(VEC)凋亡的角度进行了实验研究,为进一步探讨血瘀证实质及分子机制。方法:以1μg/mL LPS作用于人脐静脉内皮细胞(HUVEC)24h,通过流式细胞仪检测凋亡相关基因Bc l-2与黏附分子ICAM-1的表达,通过激光共聚焦显微镜测定钙离子的动态变化,并测定培养液中生物活性物质NO、ET、SOD和MDA的变化。结果:①LPS作用HUVEC后,LPS可导致HUVEC表达的Bc l-2基因下调,ICAM-1的表达增高,胞内钙离子浓度升高,同时LPS刺激后培养液中SOD降低,MDA升高,ET-1和NO几乎同时增加。结论:1μg/mL LPS可用于建立HUVEC凋亡模型,其机理与调节凋亡相关基因、黏附分子表达及钙离子浓度有关,同时可刺激HUVEC生物活性物质的分泌。     

LPS诱导HUVEC凋亡的分子机制

目的：从脂多糖（LPS）所致血管内皮细胞（VEC）凋亡的角度进行了实验研究，为进一步探讨血瘀证实质及分子机制。方法：以1μg／mLLPS作用于人脐静脉内皮细胞（HUVEC）24h，通过流式细胞仪检测凋亡相关基因Bcl-2与黏附分子ICAM-1的表达，通过激光共聚焦显微镜测定钙离子的动态变化，并测定培养液中生物活性物质NO、ET、SOD和MDA的变化。结果：①LPS作用HUVEC后，LPS可导致HUVEC表达的Bcl-2基因下调，ICAM—1的表达增高，胞内钙离子浓度升高，同时LPS刺激后培养液中SOD降低，MDA升高，ET-1和NO几乎同时增加。结论：1μg／mL LPS可用于建立HUVEC凋亡模型，其机理与调节凋亡相关基因、黏附分子表达及钙离子浓度有关，同时可刺激HUVEC生物活性物质的分泌。