益气通痹合剂抗胶原诱导的关节炎大鼠关节滑膜血管新生作用的研究

目的:探讨益气通痹合剂抗风湿的作用及其机制。方法:以Ⅱ型胶原加完全弗氏佐剂诱导的关节炎(CIA)大鼠为类风湿性关节炎模型,通过对关节滑膜病理改变、大鼠右后足关节影像学评估及对血管内皮生长因子(VEGF)、基质金属蛋白酶-1、2、3、9(MMPs)在不同处理大鼠血清中的表达,探讨该制剂的治疗效果。结果:益气通痹合剂组的滑膜组织新生血管明显减少,与模型组比较差异显著(P<0.05),关节影像学有改善;模型组大鼠血清VEGF、MMPs活性表达明显升高,益气通痹合剂组起下调作用。结论:益气通痹合剂能改善模型大鼠的病理学及影像学改变,并通过下调大鼠血清中VEGF、MMPs的表达而抑制CIA大鼠关节滑膜的血管新生功能。     

基质金属蛋白酶在生殖中的作用与调控

在生殖过程的不同阶段，生殖系统在结构和功能上不断发生周期性的变化，其基质的水解和重建与基质金属蛋白酶(MMPs)关系密切。研究表明，MMPs可以在多种因素调节下，通过与其组织抑制因子的平衡表达在月经周期、胚泡植入与胎盘形成、分娩及分娩后子宫复旧等生殖过程中发挥重要的生理功能。     

Action mechanism of Yi Guan Jian Decoction on CCl4 induced cirrhosis in rats

Aim of study

To investigate action mechanism of Yi Guan Jian Decoction on cirrhosis induced by CCl₄ in rats.

Material and methods

CCl₄ (3 mL/kg) for the first time and then olive oil CCl₄ solution 50% (2 mL/kg) was administered hypodermically to rats twice each week for 12 weeks. At the end of 8th week, rats were randomly divided into CCl₄ control group (n = 10), Yi Guan Jian Decoction group (n = 9) and Xiao Chai Hu Decoction group (n = 9). Yi Guan Jian Decoction and Xiao Chai Hu Decoction were oral administrated per day respectively for 4 weeks, concomitantly continued CCl₄ administration. At 12th weekend, the rats were sacrificed for sampling and detection of liver function, histological changes of liver tissue, liver tissue hydroxyproline content and expression of α-SMA, CD68, MMP-13, TIMP-1, TIMP-2, Caspase-12, HGFα, MMP-2, MMP-9 and hepatocyte apoptotic index.

Results and conclusions

(1) Compared with that of normal rats, expression of α-SMA, CD68 and TIMP-1 in liver tissue of 8 week model group rats increases significantly (P < 0.01), moreover further increased in the 12 week of model group. However, MMP-13, HGFα, TIMP-2 content decreases gradually and the statistical difference is seen between each time point (P < 0.01). Activity of MMP-2, MMP-9, content of Caspase-12 and hepatocyte apoptotic index increased gradually at 4th, 8th, 12th week. (2) Compared to that of the same time point model group, activity of MMP-9 and contents of MMP-13, TIMP-2 and HGFα in Yi Guan Jian Decoction group improves significantly (P < 0.01), and activity of MMP-2 and contents of α-SMA, TIMP-1, Caspase-12 and hepatocyte apoptotic index decreases significantly (P < 0.01). This work suggests that Yi Guan Jian Decoction exerts significant therapeutic effect on CCl₄-induced cirrhosis in rats, through mechanism of inhibiting hepatocytes apoptosis and hepatic stellate cells activation, and regulating the function of Kupffer cell.

Ethnopharmacological relevance

This study investigates the mechanism of Yi Guan Jian against cirrhosis from aspect of heptocytes apoptosis and hepatic stellate cells activation. It suggest that although of unknown bioactive ingredients, mechanism of traditional Chinese medicine recipe against cirrhosis can be disclosed and of profound significance.     

VEGF在胃癌中的表达及临床意义

目的介绍VEGF在胃癌的发生、发展过程中的作用及其在胃癌治疗中的前景。方法通过查阅近期国内外文献,对VEGF在胃癌的生长、浸润和转移中的作用及VEGF在胃癌治疗中的前景进行综述和分析。结果 VEGF与胃癌的生长、浸润和转移有显著的相关性,VEGF的高度表达可促进胃癌血管和淋巴管的生长,为胃癌的生长和转移提供基础;并且VEGF能提高MMPs的活性,增加胃癌对ECM(细胞外基质)的破坏能力,从而提高胃癌的浸润能力。通过抑制胃癌的细胞分泌VEGF或降低VEGF的活性,抑制胃癌血管和淋巴管的生成,从而提高胃癌的治愈率,改善患者的预后。结论 VEGF与胃癌的发生发展有显著的相关性,则针对VEGF及其受体的治疗可能成为未来治疗胃癌的新方法,具有广阔的发展前景。     

大肠癌明胶酶和TGF-β1及其受体的表达

目的研究明胶酶（MMP-2,9）与转化生长因子（TGF-β1）及其Ⅰ型受体（TGF-β1RⅠ）在大肠癌组织中的蛋白表达及其相互关系。方法应用免疫组织化学S-P法检测89例大肠癌组织中MMP-2、MMP-9与TGF-β1、TGF-β1RⅠ蛋白的表达。结果大肠癌MMP-2、MMP-9、TGF-β1和TGF-β1RⅠ阳性率分别为67.4%、65.2%、85.4%和71.9%;MMP-2表达与肿瘤大小和淋巴结转移均呈正相关（均P〈0.01）,MMP-9表达与淋巴结转移呈正相关（P〈0.01）,TGF-β1RⅠ的表达与淋巴结转移呈负相关（P〈0．01）;TGF-β1表达状况与MMP-2和MMP-9的表达均呈显著正相关（r=0．256和0．365,P〈0．05和0．001）,TGF－β1RI和MMP-9的表达呈显著正相关（r=0．225,P〈0．05）。结论MMP－2,9的表达情况与大肠癌侵袭转移有密切关系。MMP-2,9的表达与TGF—β1、TGF-β1RI关系密切,可能在一定程度上受到TGF-β1及其受体的调控。     

阿托伐他汀减轻兔血管损伤后再狭窄机制的研究

目的观察阿托伐他汀对兔血管损伤后再狭窄的干预作用,探讨其与PKC、MMPs的关系。方法将40只健康日本大耳兔,♂,分为5组,每组8只,模型组及阿托伐他汀高(2 mg.d 1)、中(1 mg.d 1)、低(0.5 mg.d 1)剂量组均行髂动脉二次损伤造模术,假手术组仅结扎股动脉。一月后取靶血管切片HE染色,图像分析仪检测各组内膜面积、中膜面积、管腔面积、内膜增生指数及狭窄指数;免疫组化检测各靶血管MMP-2、MMP-9、PKC表达。结果经髂动脉二次损伤能成功建立血管成形术后再狭窄模型。与模型组相比,随剂量升高,阿托伐他汀各组内膜面积、中膜面积、膜增生指数及狭窄指数显著降低,管腔面积显著增加(P<0.01),与此同时,靶血管MMP-2、MMP-9及PKC表达均显著降低,差异有统计学意义(P<0.01)。结论阿托伐他汀能显著减轻兔血管成形术后再狭窄,其机制可能与通过PKC途径抑制靶血管MMPs表达有关。     

Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells through suppressing the matrix metalloproteinase-2/-9, protein kinase B (PKB) and PKC signaling pathways

Advanced cancer is a multifactorial disease which complicates treatment if the cancer cells have metastasized calling for the targeting of multiple cellular pathways. Gallic acid (GA) is known to possess multiple pharmacological activity including antitumor effects. This study investigated the mechanisms for the anticancer properties of GA on migration and invasion of human osteosarcoma U-2 OS cells. The migration and invasion in U-2 OS cells were determined by a Boyden chamber transwell assay. The expression levels and activities of MMP-2 and MMP-9 were measured by Western blotting, real-time PCR and gelatin zymography assays. All examined proteins levels from Western blotting indicated that GA decreased the protein levels of GRB2, PI3K, AKT/PKB, PKC, p38, ERK1/2, JNK, NF-κB p65 in U-2 OS cells. GA also inhibited the activities of AKT, IKK and PKC by in vitro kinase assay. GA suppressed the migration and invasive ability of U-2 OS cells, and it decreased MMP-2 and MMP-9 protein and mRNA levels and secreted enzyme activities in vitro. These results suggest that potential signaling pathways of GA-inhibited migration and invasion in U-2 OS cells may be due to down-regulation of PKC, inhibition of mitogen-activated protein kinase (MAPK) and PI3K/AKT, resulting in inhibition of MMP-2 and MMP-9 expressions.