脂氧素A4对脓毒症大鼠脑损伤的抑制作用及机制研究

目的 探究脂氧素A4对脓毒症大鼠脑损伤的抑制作用及机制研究。方法 将24只大鼠进行随机分组:正常组、模型组和脂氧素A4组,每组8只。模型组和脂氧素A4组通过盲肠结扎穿孔术建立脓毒症大鼠模型:将大鼠麻醉后,于腹部做切口,结扎盲肠远端一半,用针刺穿盲肠并从穿刺的孔中挤出一滴粪便后放回腹腔内,缝合伤口;正常组做假手术处理。模型建立后,对脂氧素A4组大鼠腹腔注射脂氧素A4(50μg/kg),对正常组和模型组大鼠腹腔注射等体积生理盐水。给药后对大鼠进行神经功能评定,以Longa 5分为标准。评估各组血清中肿瘤坏死因子α(TNF-α)、白细胞介素-1(IL-1)、白细胞介素-6(IL-6)水平以及脑组织髓过氧化物酶(MPO)活性、脑组织含水量、脑组织病理变化、脑组织NADPH氧化酶2(NOX2)和核转录因子-κB(NF-κB)蛋白以及m RNA表达水平。结果 与正常组相比,模型组和脂氧素A4组大鼠的神经功能评分、TNF-α、IL-6、IL-1、MPO水平及脑组织含水量、脑组织病理损伤均明显升高,且脑组织NOX2和NF-κB蛋白以及m RNA表达水平均明显升高(P<0.05);与模型组相比,脂氧素A4组大鼠的神经功能评分、TNF-α、IL-6、IL-1、MPO水平、脑组织含水量均明显下降,大鼠脑组织病理损伤减轻,脑组织NOX2和NF-κB蛋白以及m RNA表达水平均明显降低(P<0.05)。结论 脂氧素A4能够有效抑制大鼠体内脑组织NOX2和NF-κB蛋白以及m RNA表达,降低TNF-α、IL-6、IL-1、MPO水平,抑制体内的氧化应激反应,减轻脓毒症大鼠的脑损伤。

茶氨酸衍生物茶溴香酰胺脂质体对人肺癌细胞生长和迁移的抑制作用

为了探索研究茶氨酸衍生物茶溴香酰胺制备的脂质体(TBrC-L)对人非小细胞肺癌A549细胞生长和迁移的抑制作用与其分子机制,采用薄膜分散法制备了TBrC-L,通过MTT法检测不同浓度的TBrC-L对人肺癌A549细胞生长的抑制作用;使用流式细胞术检测TBrC-L对人肺癌A549细胞凋亡的诱导作用;利用Transwell chamber法观察TBrC-L对人肺癌A549细胞迁移作用的影响;应用蛋白质印迹法检测人肺癌A549细胞中与凋亡和生长密切相关蛋白的表达和药物可能的作用靶点。实验结果显示,TBrC-L对人肺癌A549细胞生长和迁移有显著的抑制作用,促进肿瘤细胞凋亡、抑制肿瘤细胞生长和迁移可能是其抗人肺癌作用的重要机制,其作用的分子机制涉及到抑制EGFR、VEGFR1、VEGFR^2和Met受体介导的Akt和NF-κB信号传导通路,本研究结果提示,TBrC-L具有应用于临床治疗和(或)辅助治疗人肺癌的潜力。

茶氨酸衍生物TClC脂质体对雌激素受体阳性的乳腺癌细胞生长和迁移的抑制作用

为研发抗癌新药,使用茶氨酸衍生物茶氯香酰胺TClC制备纳米脂质体(TClC-L),研究TClC-L对雌激素受体阳性的人乳腺癌MCF-7细胞生长和迁移的抑制作用,并深入探究可能的作用机制。分别采用MTT和Transwell chamber实验方法探究各浓度TClC-L对MCF-7细胞的生长和迁移的抑制作用;使用流式细胞术(FCM)检测TClC-L对MCF-7细胞凋亡的影响;应用Western blotting检测MCF-7细胞生长和迁移有关蛋白和酶的表达。实验结果显示,TClC-L对MCF-7细胞生长和迁移有显著的抑制、对癌细胞的凋亡表现促进作用;TClC-L明显下调受体蛋白p-VEGFR^2、Met和ER-α、抗凋亡蛋白Bcl-2、Cyclin D1、Akt和NF-?B的表达,上调促凋亡蛋白Bax、Caspase-3、p53和p21的表达。TClC-L作用的分子机制可能与抑制VEGFR/Met/ER-α-Akt/NF-?B信号传导通路有关。本研究显示了TClC-L有潜在的治疗雌激素受体阳性乳腺癌的作用。

Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity

AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.

The inhibiting effects of Laggera alata flavone on human ovarian cancer HO-8910 cells proliferation and its mechanism in vitro

The purpose of this study was to investigate the effect of Laggera alata flavonen （LAF） on the inhibit- ing effect of human ovarian cancer HO-8910 cells proliferation and its possible mechanism in vitro. Methods： Human ovarian cancer HO-8910 cells were cultured in vitro. Inhibitory effect of LAF on the viability of HO-8910 cells was evaluated by the MTT assay. Apoptotic effect of different concentrations of LAF on HO-8910 cells was assessed by AO/EB staining and FCM with propidium iodide （PI） staining. Expression of proteins related to apoptosis was analyzed by Western blot. Results： LAF significantly inhibited the viability of HO-8910 cells proliferation in a dose-dependent and time-dependent manner, there were statistical significance compared with NS group （P 〈 0.05）, and the ICso was 4.28 pg/mL for 48 h. The cells treated with LAF showed typical morphological change and apoptotic rate increased by FCM in a dose-dependent, and there was notable dif- ference compared with NS group （P 〈 0.05）. Western blot showed that expression of Fas, caspase-8, tBid and Cyto-c proteins were up-regulated after treatment with LAF for 48 h in a concentration dependent. Conclusion： LAF could inhibit HO-8910 cells proliferation and induce apoptosis, which may be through the pathway of death receptor in vitro.

STUDY ON INHIBITION OF PANCREATIC EXOCRINE SECRETION BY SOMATOSTATIN IN RATS

We used a potent and specific monoclonal antibody to somatostatin to test the physiologic inhibitory role of the tetradecapeptide somatostatin on pancreatic secretion.Somatostatin immunoneutralization increased both the total amylase and volume of pancreatic secretion.Cholecystokinin-A receptor antagonism abolished the stimulatory effect of somatostatin immunoneutralization.We conclude that somatostatin tonically inhibits pancreatic secretion in fasted rats via inhibition of the release or action of cholecystokinin.Furthermore,the source of these peptides is likely islet delta cells and intrapancreatic neurons,respectively.

Therapeutic effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis

Objective: To assess the therapeutic effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis (SAP). Methods: Forty-two SD rats were randomly divided into 3 groups: healthy controls (HC, n=6); SAP-S group (n=18); SAP-ICE-I group (n=18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bili-pancreatic duct in SD rats. HC rats underwent same surgical procedures and duct cannulation without sodium taurocholate. In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis, which was repeated after 12 h. In SAP-ICE-I group, rats were firstly given ICE inhibitor intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, this was repeated at 12 h. Survied rats were killed at certain time points, and all samples were obtained for subsequent analysis. Results: The serum levels of ALT, AST and IL-1β in SAP-S group were (215.50±58.52)U/L, (372.17±38.05)U/L, (276.77±44.92)pg/ml at 6 h, (396.67±70.29)U/L, (548.50±75.29)U/L, (308.99±34.95)pg/ml at 12 h, (425.17±86.33)U/L, (665.83±84.05)U/L, (311.60±46.51)pg/ml, respectively, which were increased significantly (P<0.01, vs HC). In SAP-ICE-I group, their levels were decreased significantly (P<0.01, vs SAP-S). Intrahepatic expressions of Caspase-1, IL-1β and IL-18 mRNA could be observed in HC, which were increased significantly in SAP-S group (P<0.01, vs HC). The expressions of IL-1β and IL-18 mRNA were decreased significantly in SAP-ICE-I group (P<0.01, vs SAP-S), whereas Caspase-1 mRNA expressions had no significant differences (P>0.05). Caspase-1 inhibition had no effect on the severity of liver tissue damage. Conclusion: Caspase-1 activate cytokines, IL-1β and IL-18, play a pivotal role in the course of liver injury in SAP. Caspase-1 inhibitor can improve liver functions effectively.

植物次生代谢产物来源的α-葡萄糖苷酶抑制剂研究进展

α-葡萄糖苷酶抑制剂是20世纪70年代后期研究开发出来的一类新型口服降血糖药物,通过降低餐后血糖浓度,有效控制血糖水平,从而减少糖尿病并发症的发生。研究表明,植物次生代谢产物具有丰富的生物学功能,如降血糖、降血脂、抗肿瘤、增强机体免疫力等。该文对具有抑制α-葡萄糖苷酶活性作用的植物次生代谢产物的来源及其作用机制进行了综述。旨在为寻求安全、高效的植物次生代谢产物来源的α-葡萄糖苷酶抑制剂提供参考。

THE MECHANISM OF INHIBITION OF DNA SYNTHESIS BY HHO7A,ADERIVATIVE OF HAINANENSINE

The synthesis Of DNA, RNA and protein in L121O cells was inhibited by HHO7A in a dose-dependentand time-dependent way. HHO7A shOwed much stronger inhibitory effect on [3H]-thymidine incorporationthan that on [3H]-uridine or [3H]-tyrosine incorporation. The methods of shift of absorption spectrum,shift of fluorescence emission spectrum and excitation spectrum, and isotope technique were used to investigate the mechanism of actiOn of HHO7A on DNA synthesis. The results suggested thaT the action ofHHO7A on DNA synthesis was nOt probably due to direct damage to the DNA template, it might mainlyact by interfering with the metabolism of DNA.