p38丝裂原活化蛋白激酶信号转导通路在严重烧伤大鼠枯否细胞肿瘤坏死因子α和白细胞介素1β产生中的作用

目的 探讨p38丝裂原活化蛋白激酶(MAPK)信号转导通路在严重烧伤大鼠枯否细胞(KCs)促炎性细胞因子肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)产生中的作用。方法 健康成年的雄性SD大鼠32只,随机分为：假烫组;假烫 SB203580组;烧伤对照组;烧伤 SB203580组,每组8只。假烫或烧伤24h后分离出肝脏KCs,培养18h后加入50ng／ml的LPS进行刺激,18h后取上清液,用酶联免疫吸附法(ELISA)测定TNF-α和IL-1β的含量,并收集KCs,实时逆转录聚合酶链反应检测KCs内TNF-α和IL-1β mRNA表达的改变,蛋白印迹(Western blot)法检测KCs中p38MAPK和JNK活性的变化。结果 烧伤大鼠分离出的KCs培养上清液中TNF-α和IL-1β含量、KCs中TNF-α和IL-1β mRNA的表达均较假烫组的明显增强,同时KCs中p38 MAPK活性和JNK活性升高,SB203580能显著抑制大鼠KCs上清液中TNF-α和IL-1β含量、KCs中TNF-α和IL-1β mRNA的表达和p38MAPK活性的升高,对JNK活性无影响。结论p38MAPK信号转导通路介导了严重烧伤大鼠KCs促炎性细胞因子TNF-α和IL-1β的产生。     

Interiotherins C and D,two new lignans from Kadsura interior and antitumor-promoting effects of related neolignans on Epstein-Barr virus activation

Two new lignans, interiotherins C (1) and D (2), together with the known compounds interiorin (3), heteroclitin F (4), neokadsuranin (5), heteroclitin D (6), kadsurin (7), gomisin A (8), schisandrin C (9), interiotherin A (10), angeloylgomisin R (11), gomisin G (12), interiotherin B (13), and gomisin C (14), were isolated from the stems of Kadsura interior. The structures and stereochemistries of the new compounds were determined from mass, CD, and NMR spectral data. Fourteen neolignans were screened as potential antitumor promoters by examining their ability to inhibit Epstein-Barr virus early antigen (EBV-EA) activation (induced by 12-O-tetradecanoylphorbol-13-acetate) in Raji cells. Neokadsuranin (5) and schisandrin C (9) were the most potent compounds. These data suggest that some neolignans might be valuable antitumor promoters or chemopreventors.     

CTLA4-Ig-modified dendritic cells inhibit lymphocyte-mediated alloimmune responses and prolong the islet graft survival in mice

The induction of antigen specific tolerance is critical for prevention and treatment of allograft rejection. In this study, we transfected CTLA4-Ig gene into dendritic cells (DCs), and investigated their effect on inhibition of lymphocyte activity in vitro and induction of immune tolerance on pancreatic islet allograft in mice. An IDDM C57BL/6 murine model induced by streptozotocin is as model mouse. The model mice were transplanted of the islet cells isolated from the BALB/c mice to their kidney capsules, and injected of CTLA4-Ig modified DCs (mDCs). The results showed that mDCs could significantly inhibit T lymphocyte proliferation and induce its apoptosis; whereas, unmodified DCs (umDCs) promoted the murine lymphocyte proliferation. Compared with injection of umDCs and IgG1 modified DCs, the injection of mDCs prolonged IDDM mice's allograft survival, and normalized their plasma glucose (PG) levels within 3 days and maintained over 2 weeks. The level of IFN-gamma was lower and the level of IL-4 was higher in mDCs treated recipient mice than that in control mice, it indicated that mDCs led to Th1/Th2 deviation. After 7 days of islet transplantation, HE stain of the renal specimens showed that the islets and kidneys were intact in structure, and islet cells numbers are increased in mDCs treated mice. Our studies suggest that DCs expressing CTLA4-Ig fusion protein can induce the immune tolerance to islet graft and prolong the allograft survival through the inhibition of T cell proliferation in allogeneic mice.     

Filiasparosides A-D, cytotoxic steroidal saponins from the roots of Asparagus filicinus

Four new steroidal saponins, filiasparosides A-D (1-4), together with known aspafiliosides A (5) and B (6) were isolated from the roots of Asparagus filicinus. The structures of these new compounds were elucidated by detailed spectroscopic study and chemical analysis. Compounds 1-6 were cytotoxic against human lung carcinoma (A549) and breast adenocarcinoma (MCF-7) tumor cell lines with EC(50) values of 2.3-16.8 microg/mL. Compound 3 showed the most potent cytotoxicity, with EC(50) values of 2.3 and 3.0 microg/mL toward A549 and MCF-7 cell lines, respectively.     

地血香乙醇提取物对小鼠肝细胞中抗氧化酶活性的影响

本文报道地血香乙醇提取物和其主要成分Kadsurin对小鼠肝细胞中抗氧化酶活性的影响。地血香和Kadsurin能够明显增加肝细胞中超氧物歧化酶和过氧化氢酶的活性，而对谷胱甘肽过氧化物酶活性的影响无统计学意义。     

Three new isoprenylated flavonoids from the roots of Sophora flavescens

Three new flavonoids isoprenylated as 2,2-dimethyl-dihydropyran groups, named sophoranodichromanes A-C (1-3), have been isolated from the roots of Sophora flavescens, together with the known compounds, chrysophanol (4), soyasapogenol B (5) and β-sitosterol (6). Their structures have been elucidated by spectroscopic methods.     

Insulin resistance following thermal injury: an animal study

The aim of this study was to investigate the changes of glucose tolerance, insulin sensitivity, and euglycemic-hyperinsulinemic glucose clamps following a 30% TBSA full thickness third degree burn in rats. Sprague-Dawley rats weighing 160-170g received 30% TBSA full thickness third degree burn by immersing the back of trunk for 12s in a boiling water bath under anesthesia. Weight- and time-matched sham burn group (control) was treated in the same manner as the trauma group, except that they were immersed in a room-temperature water bath. After 12h overnight fasting, plasma insulin concentration was determined by ELISA using rat-insulin enzyme immunoassay kit (SPI-BIO) and blood glucose was assayed by glucose analyzer at 3 days after burn. Insulin sensitivity index was calculated by using slightly modified formula. The rat was injected with 5% glucose (2g/kg body weight, intraperitoneally) to observe the change of glucose tolerance at 3 days after burn. Euglycemic-hyperinsulinemic glucose clamps were performed at 4 days after burn. Insulin sensitivity index of burn group was significantly reduced compared with control group at 3 days after burn (0.58+/-0.23 versus 1.23+/-0.16, P<0.01). The significant difference of glucose tolerance was observed between the two groups and the glucose infused rate measured in burned rats was significantly decreased compared with that in control at 4 days after injury (7.23+/-1.35 versus 12.31+/-0.54, P<0.01). Conclusion: Burn causes the significant change of glucose metabolism and results in insulin resistance in rats.     

Asparosides A and B,two new steroidal saponins from Asparagus meioclados

Asparosides A ( 1 ) and B ( 2 ), two new saponins, were isolated from the roots of Asparagus meioclados . On the basis of chemical and spectroscopic evidence, their structures were elucidated as 23- O - f -arabinopyranosyl-(5 g ,25s)-spirostan-3 g ,23 f -diol-3- O -[ g - d -xylopyranosyl(1 M 4)]- g - d -glucopyranoside and 26- O - g -glucopyranosyl-5 g -furost-20(22)-ene-3 g ,26-diol-3- O -[ g - d -xylopyranosyl(1 M 4)]- g - d -glucopyranoside, respectively.     

Viola yedoensis liposoluble fraction ameliorates lipopolysaccharide-induced acute lung injury in mice

Viola yedoensis is a component of traditional Chinese herb medicine for inflammatory diseases. Chemical constituents of V. yedoensis have been shown to possess antibacterial, anti-HIV, and anticoagulant effects in experimental research; however, their anti-inflammatory properties remain to be demonstrated. In this study, a mouse model of lipopolysaccharide (LPS)-induced acute lung injury was used to investigate the effect of petroleum ether fraction of V. yedoensis (PEVY) on inflammation in vivo. After being shown to have anti-complementary activity in vitro, PEVY was orally administered to the mice at doses of 2, 4, and 8 mg/kg. Treatment with PEVY significantly decreased the wet-to-dry weight ratio of the lung, total cells, red blood cells, protein concentration, and myeloperoxidase activity in bronchoalveolar lavage fluid. PEVY markedly attenuated lung injury with improved lung morphology and reduced complement deposition. In addition, PEVY suppressed the expression of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6. Taken together, PEVY protects the lung from acute injury, potentially via inhibiting the activation of the complement system and excessive production of proinflammatory mediators.     

补体抑制活性柴胡多糖及其作用靶点研究(英文)

目的:从北柴胡根中分离表征具有抗补体活性的多糖成分。方法:以抗补体活性为导向从北柴胡根水提物中分离纯化活性多糖;化学和谱学方法表征多糖的理化性质;采用体外细胞溶血试验法测定抗补体活性;并利用补体成分缺失血清鉴定补体激活过程中的作用靶点。结果:获得一个均一多糖BC-PS2,是一个具分支结构的杂多糖,平均分子量2000KDa,其单糖摩尔比为:葡萄糖/阿拉伯糖/半乳糖/甘露糖=3.5:2.4:2.0:1.0,并含有少量的鼠李糖和木糖以及蛋白(1.11%);单糖的主要连接方式包括:末端、1,3-、1,6-和1,3,6-连接的葡萄糖,末端、1,5-连接的阿拉伯糖,末端、1,4-、1,6-和1,4,6-连接的半乳糖,末端、1,4-和1,4,6-连接的甘露糖;BC-PS2对补体激活的经典和旁路途径均有抑制作用,CH50和AP50分别为(0.222±0.013)和(0.356±0.032)mg·mL-1;靶点研究结果表明BC-PS2作用于补体成分C1q,C2和C9。结论:BC-PS2是一个具有抗补体活性的多糖成分,应该是柴胡治疗与补体过度激活相关疾病的药效成分之一。