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991.
目的探讨痹颗粒对RA-MsPGN大鼠模型肾组织PTK活性的影响,治疗RA-MsPGN的作用机制。方法按照Phospho Safe TM ExtR Action Reagent试剂盒提取蛋白质,按照K-LISA PTK Screening Kit试剂盒测定蛋白酪氨酸激酶(PTK)活性,并根据检测试剂盒提供的标准品直线回归方程计算PTKs的含量。结果RA-MsPGN模型大鼠与正常组相比肾组织PTK含量显著升高(P<0.001),雷公藤多苷片和痹颗粒各剂量组均能显著降低大鼠肾组织PTK含量(P<0.05或0.01)。结论痹颗粒对RA-MsPGN大鼠肾组织PTK活性有明显抑制作用,其治疗作用有可能是通过对PTK的作用而实现的。 相似文献
992.
目的从PI3K/AKT信号通路研究三七总皂苷(panax notoginseng saponins,PNS)预防糖尿病大血管病变的机制。方法雄性SD大鼠分为对照组、模型组和治疗组,模型组和治疗组大鼠高脂饲料喂养6周后给予链脲佐菌素单次腹腔注射(30 mg·kg-1体质量)建立2型糖尿病模型,成模后治疗组给予PNS灌胃干预(100mg·kg-1体质量)。血糖仪检测大鼠空腹尾静脉血糖(FBG),ELISA法测定血清空腹胰岛素(FINS)和糖化血红蛋白(GHbA1c)水平,苏木素-伊红(HE)染色观察腹主动脉病理形态改变,荧光定量PCR检测腹主动脉标记物MMP2、MMP9、CD34、VEGF及PI3K、AKT mRNA相对表达,Western Blot法观察PI3K和AKT蛋白表达情况。结果模型组和治疗组大鼠在STZ注射造模后,FBG均显著高于对照组(P<0.01和P<0.01),两组间差异无统计学意义(P>0.05)。模型组和治疗组血清INS均显著高于对照组(P<0.01和P<0.01),治疗组INS显著低于模型组(P<0.05)。HE染色显示,与对照组比较,模型组动脉壁变薄,平滑肌细胞增多,排列紊乱,内膜不光滑;治疗组较模型组明显改善。模型组MMP2、MMP9表达较对照组显著上调(P<0.05和P<0.01),治疗组MMP9较模型组显著下调(P<0.01)。模型组CD34、VEGF表达较对照组显著上调(P<0.05和P<0.01),治疗组CD34较模型组显著下调(P<0.05)。模型组大鼠PI3K表达较对照组显著上调(P<0.05),治疗组PI3K表达较模型组显著下调(P<0.05)。模型组PI3K蛋白、p-AKT蛋白表达均显著高于对照组(P<0.01和P<0.01),治疗组PI3K、p-AKT均显著低于对照组(P<0.01和P<0.05),模型组p-AKT/AKT显著高于对照组(P<0.05),治疗组p-AKT/AKT较模型组有显著降低趋势,且与对照组差异无统计学意义。结论PNS可能通过下调PI3K/AKT信号通路预防糖尿病大血管病变。 相似文献
993.
Characterization of tetrandrine,a potent inhibitor of P-glycoprotein-mediated multidrug resistance 总被引:8,自引:0,他引:8
Fu L Liang Y Deng L Ding Y Chen L Ye Y Yang X Pan Q 《Cancer chemotherapy and pharmacology》2004,53(4):349-356
Multidrug resistance (MDR) is one of the main obstacles in tumor chemotherapy. A promising approach to solving this problem is to utilize a nontoxic and potent modulator able to reverse MDR, which in combination with anticancer drugs increases the anticancer effect. Experiments were carried out to examine the potential of tetrandrine (Tet) as a MDR-reversing agent. Survival of cells incubated with Tet at 2.5 mol/l for 72 h was over 90%. Tet at 2.5 mol/l almost completely reversed resistance to vincristine (VCR) in KBv200 cells. Tet at a concentration as low as 0.625 mol/l produced a 7.6-fold reversal of MDR, but showed no effect on the sensitivity of drug-sensitive KB cells in vitro. In the KBv200 cell xenograft model in nude mice, neither Tet nor VCR inhibited tumor growth. However, VCR and Tet combined inhibited tumor growth by 45.7%, 61.2% and 55.7% in three independent experimental settings. In the KB cell xenograft model in nude mice, Tet did not inhibit tumor growth, but VCR and the combination of VCR and Tet inhibited tumor growth by 40.6% and 41.6%, respectively. Mechanism studies showed that Tet inhibited [3H]azidopine photoaffinity labeling of P-gp and increased accumulation of VCR in MDR KBv200 cells in a concentration-dependent manner. The results suggest that Tet is a potent MDR-reversing agent in vitro and in vivo. Its mechanism of action is via directly binding to P-gp and increasing intracellular VCR accumulation.Abbreviations DMSO
Dimethyl sulfoxide
- FBS
Fetal bovine serum
- MDR
Multidrug resistance
- MTT
3-(4,5-Dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide
- PBS
Phosphate-buffered saline
- P-gp
P-glycoprotein
- SDS
Sodium dodecyl sulfate
- Tet
Tetrandrine
- VCR
Vincristine 相似文献
994.
目的:构建IFN-α2a-GFE-1融合蛋白基因表达载体,获得高质量生物产品。方法:应用聚合酶链式反应技术(PCR)对干扰素(IFN)α2a3'端酶切位点进行改造,人工合成编码能特异性高效结合肺组织的GFE-1寡核苷酸片段,二者连接后克隆入pGEM3Zf质粒,进行序列分析,将融合蛋白基因克隆入pBV220表达载体,在大肠杆菌中表达,对IFN-α2a-GFE-1表达产物纯化、鉴定及体外活性检测。结果:利用PCR的方法成功地改造了IFN-α2a3'端酶切位点,成功的将GFE-1多肽与IFN-α2a3'端连接,构建了IFN-α2a-GFE-1融合蛋白的基因克隆载体pGEM3Zf-GFE-1,DNA测序完全正确。构建了IFN-α2a-GFE-1融合蛋白基因原核表达载体pBV220-IFN-α2a-GFE-1,经温度诱导在大肠杆菌中有效表达。纯化了IFN-α2a-GFE-1融合蛋白,SDS-PAGE凝胶电泳检测纯度大95%,比活性达5.8×109U/mg。结论:IFN-α2a-GFE-1融合蛋白基因的成功克隆、表达、纯化和活性测定,为研制一种具有导向性治疗肺癌、肺纤维化等疾病的有效药品奠定基础。 相似文献
995.
Reduction of Foxp3+ T cell subsets involved in incidence of chronic graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation 下载免费PDF全文
Yongxian Hu Qu Cui Yishan Ye Yi Luo Yamin Tan Jimin Shi He Huang 《Hematological oncology》2017,35(1):118-124
Foxp3+ T cells (CD4+ Tregs and CD8+ Treg) have been demonstrated to play roles in the maintenance of tolerance after allogeneic hematopoietic stem cell transplantation (Allo‐HSCT). We have found that Foxp3+ γδTCR+ Treg cells (γδTregs) exerted regulatory functions. In the current study, patients were recruited and divided as non‐cGVHD, limited cGVHD and extensive cGVHD groups. Healthy volunteers were recruited as healthy group. Treg cells were evaluated by flow cytometry. Serum cytokine levels of IL‐2, tumour necrosis factor‐α, interferon‐γ and transforming growth factor‐β1 (TGF‐β1) were evaluated by ELISA. The results showed that percentages of CD4+ Tregs, CD8+ Tregs and γδTregs were all significantly increased in non‐cGVHD group compared with those in healthy group, limited cGVHD group and extensive cGVHD group. Moreover, compared with extensive cGVHD group, percentages of these three types of Tregs were significantly increased in limited cGVHD group. The levels of TGF‐β1 increased dramatically in non‐cGVHD group compared with other groups. Spearman's correlation analysis revealed that the increased levels of TGF‐β1 and IL‐2 were positively associated with increased Treg subsets, indicating that TGF‐β1 and IL‐2 participated in the expansion process of Foxp3+ Tregs in vivo. Our findings support that increasing the number of Tregs following allo‐HSCT would be a preferential strategy for controlling cGVHD. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
996.
997.
目的:探讨根治性膀胱切除术(RC)后早期并发症(术后90 d内)及其相关的危险因素.方法:收集我院泌尿外科2013年1月至2016年1月期间共185例因膀胱癌行根治性膀胱切除术(RC)的临床资料,术后90天内对患者随访,并应用X2检验和Logistic回归分析术后常见早期并发症的危险因素.结果:术后90天内185位患者中有74位(40.0%)出现了不同的早期并发症,常见并发症依次为肠梗阻、泌尿系感染、切口方面并发症.在回归分析中发现年龄(≥65岁)、肥胖(BMI≥25 kg/m2)、术中输血、手术方式、手术时间、糖尿病是发生RC术后早期并发症的危险因素.结论:根治性膀胱切除术术后早期并发症发生率较高,其中肠梗阻、泌尿系感染、切口方面并发症较常见,正确的围手术期处理及充足的术前准备是降低膀胱癌根治术术后早期并发症的关键. 相似文献
998.
999.
Jiao Peng Julia Y. Tsang Derek H. Ho Ruizhong Zhang Haitao Xiao Daxu Li Jiang Zhu Fenghua Wang Zhaoxiang Bian Vincent C. Lui Aimin Xu Paul K. Tam Jonathan R. Lamb Huimin Xia Yan Chen 《International journal of cancer. Journal international du cancer》2015,137(4):848-858
The plasticity of macrophages with selective functional phenotypes partially arises in respective to their microenvironment. Tumor‐associated macrophages (TAMs) may promote disease progression with tumor specific manner. Here we report that in pediatric malignant soft‐tissue tumors, the presence of TAMs and expression of adiponectin (APN) are heterogeneous. Both APN and TAMs had high expression in rhabdomyosarcoma, especially in the malignant subtype, alveolar rhabdomyosarcoma. To investigate the mode of action of APN on TAM activation, a murine MN/MCA1 sarcoma model was used. The Results revealed that exogenous APN had no effect on MN/MCA1 proliferation but tumor size was markedly reduced in apn?/? mice versus WT controls. The accumulation of TAMs in apn?/? mice was also reduced which correlated to downregulated serum levels of MCP‐1. Likewise, TAMs in apn?/? mice exhibited a M1‐like phenotype, characterized by increase in MHC IIhigh population and M1 phenotypic markers, such as iNOS gene and serum TNF‐α accompanied by a decrease in M2 markers, namely YM1 gene and serum IL‐10. In addition, APN deficiency increased the number of CD4+ T cells, CD8+ T cells and NK cells in tumors and reduced tumor metastasis. The altered phenotype of TAMs in apn?/? mice was associated with a marked decrease in phospho‐p38 and treatment with a p38 MAPK inhibitor significantly reduced tumor size and increased MHC II expression on TAMs in WT mice, implying p38 MAPK signaling pathway may contribute to APN‐mediated TAM polarization. Collectively, our findings suggest that APN may have a potential role in regulating soft tissue sarcoma growth. 相似文献