PCNA、P21和COX-2在尖锐湿疣中的表达及其意义

目的:研究尖锐湿疣组织中增殖细胞核抗原(PCNA)、P21及环氧化酶-2(COX-2)蛋白表达及其意义。方法:应用免疫组化SP法对30例尖锐湿疣组织及10例正常组织中PCNA、P21及COX-2蛋白进行检测。结果:30例尖锐湿疣组织中PCNA、P21阳性表达较正常对照组有不同程度的增加,有统计学意义;COX-2蛋白在尖锐湿疣组织中阳性表达率13.3%(4/30),正常组织无阳性表达(0/10),两者之间无显著性差异(P>0.05);尖锐湿疣组织中PCNA与P21表达之间无相关性(r=0.196,P>0.05)。结论:PCNA、P21过表达与尖锐湿疣角质形成细胞自限性增殖密切相关。

Cox-2和P-21蛋白在子宫内膜癌中的表达及意义

目的探讨子宫内膜癌中P-21蛋白和环氧化酶-2(Cyclooxygenase-2,COX-2)的表达和意义。方法采用免疫组织化学中的SP法对对照组中20例正常的子宫内膜组织患者、非典型增生组中的7例子宫内膜出现非典型增生组织患者以及子宫内膜癌组中的55例子宫内膜癌组织患者中P-21蛋白及COX-2的表达情况进行检测。结果与非典型增生组和子宫内膜癌组相比,对照组中患者P-21蛋白的阳性表达率显著较高(P<0.05),而对照组中Cox-2的阳性表达率显著较非典型增生组和子宫内膜癌组低(P<0.05);在手术-病理分期和分化程度,以及淋巴结出现转移等宫内膜癌组织的相关方面,P-21蛋白的阳性率具有明显差异(P<0.05);Cox-2阳性率在子宫内膜癌组织的手术-病理分期、分化程度、肌层浸润方面差异有统计学意义(P<0.05),子宫内膜癌组织P-21蛋白阳性表达率与Cox-2阳性呈负相关(r=-0.498,P=0.000)。结论 P-21蛋白和Cox-2异常表达可能在子宫内膜癌的发生、发展中起重要作用。

COX-2在大鼠全肝/部分肝移植缺血再灌注损伤中的表达

目的探讨COX-2在大鼠全肝/部分肝移植缺血再灌注损伤(IRI)模型中的表达及其意义。方法雄性Wistar大鼠随机分成3组:正常对照组(O);全肝移植组(LT);50%部分肝移植组(PLT)。逆转录-聚合酶链反应(RT-PCR)半定量检测COX-2 mRNA的表达;免疫组织化学显示COX-2阳性细胞分布规律;酶联免疫吸附试验(ELISA)检测血清TNF-α和IL-10水平。结果COX-2的表达为肝移植缺血再灌注损伤机制所必需,IRI损伤较重的部分肝移植组(PLT)伴随有较高水平的COX-2 mRNA表达;且存在其表达量随再灌注后时间点的延长而逐渐下降的规律。结论COX-2参与了肝移植缺血再灌注损伤,是移植物IRI的重要效应分子,是IRI的参与者之一。

COX-2和Ki67在鲍恩病皮损中的表达

目的研究COX-2和Ki67在鲍恩病皮损中的表达情况,并探讨两者之间的关系。方法应用免疫组化SP染色法对27例鲍恩病患者皮损及15份正常皮肤组织进行COX-2和Ki67染色。结果 COX-2与Ki67在正常皮肤组织中表达非常低,而在鲍恩病皮损中染色强度显著增高(P<0.05)。COX-2与Ki67在鲍恩病皮损中的表达水平呈显著正相关(r=0.451,P<0.05)。结论 COX-2与鲍恩病的发生密切相关,过度表达的COX-2蛋白可能参与肿瘤细胞的增生过程。

Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: A review and report of personal experience

Selective cyclooxygenase （COX）-2 inhibitors （coxibs） were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs （NSAIDs）. However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis （FAP）, which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration （FDA） immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors.

Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats

Objective： To examine modulations caused by cyclooxygenase-2 （COX-2） inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods： Celecoxib （a COX-2 inhibitor） was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mlPSCs （miniature GABAergic inhibitory postsynaptic currents） of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of c^-subunit of y-amino butyric acid （GABAA） receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase （MAPK/ERK） activity were detected by Western blotting. Results： Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABAA receptors. NS-398 （N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide）, another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion： The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.

Expressions of cyclooxygenase-2 and matrix metalloproteinase-9 in cervical carcinoma and their clinical significance

Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detect the expres- sions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE). The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results: The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% (64/72) in group ICC and 12.5% (2/16) in group NCE, P = 0.000; MMP-9: 94.4% (68/72) in group ICC and 43.8% (7/16) in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis (r = 0.296, P = 0.012) and stromal invasion (r = 0.257, P = 0.029). The expression of MMP-9 was positively correlated with FIGO stage (r = 0.329, P = 0.005) and histological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). Conclusion: The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.

Design, Synthesis and in vitro Evaluation of Thiazole Derivatives of Ibuprofen as Cyclooxygenase-2 Inhibitors

A series of thiazole derivatives of ibuprofen, as cyclooxygenase-2 Inhibitors, were designed, synthesized and in vitro evaluated.

Protective effect of notoginsenoside and tanshinone IIA on inflammation-related colorectal cancer mice and the inhibition effect on COX-2 expression

Objective To explore the preventive effects and possible mechanisms of action of notoginsenoside(NGS)and tanshinone IIA(TSN)in inflammation-related colorectal cancer(IRCC)in mice.Methods Eighty-eight male C57BL/6 mice were randomly assigned to 11 groups(n=8 each group).Azomethane oxide+dextran sulfate(AOM+DSS)model control(model),NGS lowdose(l-NGS),NGS medium-dose(m-NGS),NGS high-dose(h-NGS),TSN low-dose(l-TSN),TSN medium-dose(m-TSN),TSN high-dose(h-TSN),(NGS+TSN)low-dose[l-(NGS+TSN)],(NGS+TSN)medium-dose[m-(NGS+TSN)],(NGS+TSN)high-dose[h-(NGS+TSN)],and blank groups were established.The first 10 groups were intraperitoneally injected with AOM to induce inflammatory colon cancer,whereas the blank group was intraperitoneally injected with 0.9%NaCl solution.The first 10 groups drank a 2.5%sodium DSS aqueous solution continuously from day 5 for three cycles(one cycle:five days,every three weeks),and the blank group was allowed free access to water.Drug groups were administered NGS(low,medium,or high dose),TSN(low,medium,or high dose),or NGS+TSN(low,medium,or high dose),and the model and blank groups were administered saline by lavage until the end of the experiment.The general activity,body weight,and survival rate of and incidence of adenocarcinoma in mice were detected and the expression of cyclooxygenase 2(COX-2)was detected by immunohistochemistry.Results(1)The survival rate of mice with IRCC in the h-NGS,m-TSN,h-TSN,m-(NGS+TSN),and h-(NGS+TSN)groups was significantly increased than that in other groups(P<0.05).(2)The incidence of tumors in the h-(NGS+TSN),m-TSN,and l-NGS groups was significantly lower than that in the model group(P<0.05).(3)The expression level of COX-2 in tumor tissues of mice in the m-(NGS+TSN)and h-(NGS+TSN)groups was significantly lower than that in the model group(P<0.05).Conclusion Tumor formation was inhibited by m-TSN and h-(NGS+TSN)treatments in mice with IRCC,and h-(NGS+TSN)treatment inhibited the COX-2 pathway.

The clinical significance of CD97, NF-kB and COX-2 ingastric MALT lymphomas

Background and Objectives: Increased expression of the CD97, nuclear factor-kB (NF-kB) and cyclooxygenase-2 (COX-2) has been found to play an important role in development of many cancers, including gastric neoplasm. However, the expression and biological behavior of CD97, NF-kB and COX-2 in gastric MALT (mucosa-associated lymphoid tissue) lymphoma has not been well investigated. Methods: The expressions of CD97, COX-2 and NF-kB in 47 cases of gastric MALT lymphoma were detected immunohistochemically, and the relevance between their expressions and the biological behavior was analyzed retrospectively. Results: 1) The expressions of CD97, NF-kB and COX-2 were 87.2%, 36.2% and 48.9%, respectively;2) The difference of CD97 expression between depth of invasion limited in mucosa and submucosa and beyond muscularis propria was significant (100.0% vs. 71.4%, P < 0.01). Moreover, the expression of nuclear CD97 between stage IIE, III, IV and stage I patients showed significant difference (96.4% vs. 73.7%, P < 0.05);3) The expression of NF-kB was significantly correlated with tumor size, depth of invasion and stage;4) The expression of COX-2 was significantly correlated with Helicobacter pylori infection, clinical stage, depth of invasion and tumor size (P < 0.05). Conclusions: Expressions of CD97, NF-κB and COX-2 were correlated with tumor invasion and metastasis in gastric MALT lymphoma.

The effects of the same target on malignant proliferation of human lung cancer cells with different expression levels of COX-2 protein

Objective: The aim of the study was to explore the effects of the same target (si-10) on lung cancer cells with different expression levels of cyclooxygenase-2 (COX-2) protein by RNAi and malignant proliferation of these cells. Methods: COX-2 was selected as the target and one siRNA expression vector with the best effect was selected and thought as the subject from three COX-2 siRNA expression vectors with human U6 promoter. The siRNA expression vector (psi-10) and the vacant vector (pEGFP) were transfected into these cells with different COX-2 expression states (801D, A549 and LTEP-A2) with lipofectamine respectively and the transfected cell strains were constructed. The change of COX-2 expression levels was examined by Western blot and RT-PCR. The effects on the proliferation of lung cancer cells were studied by cell growth curve and clonogenic assay. Results: The siRNA and U6 promoter were validated by PCR, restriction endonucleases identification and DNA sequencing and BLAST alignment and cloned into the pEGFP vector. The cell strains transfected that 801D was used as maternal line were named as 801D-p and 801D-10 respectively. The cell strains transfected that A549 was used as maternal line were named as A549-p and A549-10 respectively. The cell strains transfected that LTEP-A2 was used as maternal line were named as LTEP-A2-p and LTEP-A2-10 respectively. These cells transfected pEGFP (801D-p, A549-p and LTEP-A2-p) had the expression of GFP and 801D-10, A549-10 and LTEP-A2-10 cells had not in 24, 48 and 72 hours after transfected. The results of RT-PCR and Western blot showed the siRNA expression vector produced marked effects in two cells (A549 and LTEP-A2) expressing COX-2 and the expression of COX-2 was inhibited. But the inhibited effects were differ- ent and the expression of COX-2 was more inhibited obviously in LTEP-A2 cells than in A549 cells though the expression of COX-2 was also inhibited obviously in A549 cells. In contract to their maternal line, the levels of COX-2 mRNA of LTEP-A2-10 and A549-10 cells reduced 64.2% and 61.2% respectively; the levels of COX-2 protein reduced 60.2% and 56.2% respectively. But the levels of COX-2 mRNA and protein had not change in 801D cells not expressing COX-2. The results of cell growth curve and clonogenic assay showed the growth of LTEP-A2-10 cells slowed and the clonal formation rate reduced and the size of the colonies became small; the growth of A549-10 cells showed slow and more obviously in the cell growth curve especially. But the growth of 801D-10 cells had not obvious change. Conclusion: The si-10 target of COX-2 has different inhibition effects on lung cancer cells with different COX-2 expression levels and the different inhibition effects have different effects on cells malignant proliferation.

美洛昔康对急性肺损伤兔肺组织 COX －2与 PPAR －γmRNA 表达的影响

目的：观察美洛昔康对内毒素（endotoxin， ET）复制急性肺损伤（ALI）时兔肺组织环氧合酶－2（ cyclooxygenase －2， COX －2）和过氧化物酶增殖体激活受体－γ（ peroxisome proliferation activated receptor －γ， PPAR－γ） mRNA变化的影响，来探讨其对ALI保护作用的机制。方法将24只日本大耳白兔随机分为生理盐水对照组（ A组）、内毒素致伤组（ B组）、美洛昔康干预组（C组）。用ET（700μg／kg）静脉注射复制兔子ALI模型，美洛昔康（2．5 mg／kg）进行干预，观测兔动脉血气、光镜肺组织病理、肺组织中COX－2 mRNA与PPAR－γmRNA的表达。结果 COX－2 mRNA 表达 B 组显著高于 A 组（P ＜0．01），C 组显著低于 B 组（P＜0．01）。PPAR－γmRNA表达B组显著低于A组（P＜0．01），C组显著高于B组（P＜0．01）。结论美洛昔康可通过下调COX－2 mRNA和上调PPAR－γmRNA的表达，在一定程度上对兔内毒素性ALI产生保护作用。

E—cadherin、P21和COX-2对食管鳞癌预后意义的研究进展

食管鳞癌（esophagealsquamouscellcarcinoma，ESCC）是常见的恶性肿瘤之一，对ESCC预后评估的常用手段是TNM分期，但临床常有预后与分期不符的现象，可能的原因除包括现有的食管癌临床分期手段有限和不准确外，还可能存在TNM定量分期诊断以外的预后影响因素。其中寻找ESCC预后判断与疗效预测分子的研究受到了广泛的重视。我们在单一手术组接受单纯手术的153例ESCC患者石蜡包埋组织切片中检测12种蛋白分子的表达，并验证它们的表达与患者预后的关系，结果发现仅有P21、E—cadherin和COX-2的表达与患者预后相关，并且是ESCC患者的独立预后因素。

喉癌手术切缘组织中p53、p21、PCNA及COX-2蛋白的表达与肿瘤局部复发的关系

目的：探讨喉癌手术切缘组织中p53、p21、PCNA及COX-2蛋白的表达与肿瘤局部复发的关系。方法：选取2005-11-2010—12期间住院的98例喉癌患者，病理检查均为早期喉鳞状细胞癌，所有患者均实施CO：激光手术方式切除，切除整块肿瘤后，留取肿瘤原发灶组织和手术切缘组织，保留5mm癌周组织作为手术切缘标本。采用SP法进行免疫组织化学检测，每3～6个月门诊或电话随访，对局部组织复发情况进行详细记录，随访3．0～4．5年。结果：①98例喉癌患者的肿瘤组织中p53、p21、PCNA及COX-2蛋白的阳性率为65．3％、52．00．4、70．4014及69．4％；手术切缘组织中p53、p21、PCNA及COX-2蛋白的阳性率为23．5％、39．8％、32．7％及30．6％；差异有统计学意义（均P〈0．05）；p53、p21、PCNA及COX-2蛋白在喉癌组织中的表达与肿瘤的分级及TNM分期无关。②98例患者随访3年以上，局部复发17例（17．3％）。切缘组织中p53、p21、PCNA及COX-2阳性表达的患者复发率高于阴性表达的患者（P〈0．05），其中p53和p21、PCNA和COX-2检测共阳性的患者复发率显著高于单阳性的患者（P〈0．05）。③p21在p53阳性切缘组织中的阳性表达显著高于其在阴性切缘组织中的表达；PCNA在p21、COX-2阳性切缘组织中的阳性表达显著高于其在阴性切缘组织中的表达（P〈0．01）；但PCNA在p53阳性切缘组织中的阳性表达与其在阴性切缘组织中的表达差异无统计学意义（P〉0．05）。结论：通过探讨p53、p21、PCNA及COX-2在喉癌细胞增生及局部复发过程中的作用，提示生化代谢与分子结构水平表达异常先于细胞形态表观的改变，建议对阳性指标进行随访检测，阳性表达的患者可采取相应的措施对症干预。

Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition

Objective: Drug-resistance and metastasis are major reasons for the high mortality of ovarian cancer(OC) patients. Cyclooxygenase-2(COX-2) plays a critical role in OC development. This study was designed to evaluate the effects of COX-2 on migration and cisplatin(cis-dichloro diammine platinum, CDDP) resistance of OC cells and explore its related mechanisms. Methods: Cell counting kit-8(CCK-8) assay was used to detect the cytotoxicity effects of celecoxib(CXB) and CDDP on SKOV3 and ES2 cells. The effect of COX-2 on migration was evaluated via the healing test. Western blot and real-time quantitative polymerase chain reaction(q PCR) were used to analyze E-cadherin, vimentin, Snail, and Slug levels. Results: COX-2 promoted drug-resistance and cell migration. CXB inhibited these effects. The combination of CDDP and CXB increased tumor cell sensitivity, reduced the amount of CDDP required, and shortened treatment administration time. COX-2 upregulation increased the expression of Snail and Slug, resulting in E-cadherin expression downregulation and vimentin upregulation. Conclusions: COX-2 promotes cancer cell migration and CDDP resistance and may serve as a potential target for curing OC.

Simultaneous determination of 35 constituents and elucidation of effective constituents in a multi-herb Chinese medicine formula Xiaoer-Feire-Kechuan

Xiaoer-Feire-Kechuan(XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,we combined quantitative analysis and bioactivity test to reveal the antiinflammatory constituents of XFK.First,UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes(covering 9 out of 11 herbs) in different XFK formulations.Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity.Then,anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay.Finally,major analytes forsythosides H,I,A(8-10),and baicalin(15)(total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities(inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK.The present study provided an effective strategy to discover effective constituents of multi-herb formulas.

lncRNA-PACER upregulates COX-2 and PGE2 through the NF-κB pathway to promote the proliferation and invasion of colorectal-cancer cells

Background p50-associated cyclooxygenase-2 extragenic RNA(PACER)is a recently identified antisense long non-coding RNA(lncRNA)located on the upstream of the promoter region of cyclooxygenase-2(COX-2).Preliminary studies have suggested that PACER is involved in the regulation of COX-2 expression in macrophagocyte and osteosarcoma cells.However,the role of this lncRNA in colorectal cancer(CRC)remains elusive.Here,we investigated the expression of PACER and its effect on cell proliferation and invasion to explore the role of PACER in CRC.Methods Real-time quantitative PCR(RT-qPCR)analysis was used to evaluate the expression of PACER in CRC tissues and cells.Methyl thiazolyl tetrazolium(MTT)analysis was then used to investigate the inhibition effect of PACER knock-down in cell proliferation.The promoting role of this lncRNA on invasion by CRC cells was analysed by wound-healing assays,colony-formation assay,and transwell assays.We then used fluorescence in situ hybridization(FISH)to establish the subcellular localization of PACER.COX-2 protein levels were quantified by Western blot analysis and grayscale scanning analysis following the knock-down of PACER.Luciferase assay was carried out to monitor the modulation of the COX-2 promoter region by PACER.Tumor xenografts models were used to investigate the impact of PACER on the tumorigenesis of CRC cells in vivo.Enzyme-linked immunosorbent assay(ELISA)was then used to quantify prostaglandin E2(PGE2)production upon knock-down of PACER.Results RT-qPCR analysis revealed that PACER was highly expressed in CRC tissues and cells,and a high PACER-expression level was associated with poor prognosis.MTT assay,wound-healing assay,colony-formation assay,and transwell assay revealed that PACER enhanced CRC-cell proliferation,invasion,and metastasis in vitro.Analysis of lncRNA localization by FISH showed that it mainly resided in the nucleus.RT-qPCR showed that PACER increased mRNA levels of COX-2.Western blot analysis demonstrated,under normal circumstances,that knock-down of PACER decreased the COX-2 protein level.In the case of p50 absence,COX-2 protein increased rapidly and remained highly expressed after knocking down PACER.Luciferase assay revealed that PACER modulated the COX-2 promoter region.Mouse xenograft models of CRC revealed that PACER promoted colorectal tumorigenesis in vivo.ELISA revealed that PACER knock-down inhibited PGE2 production.Conclusions PACER modulates COX-2 expression through the nuclear factor kappa B(NF-jB)pathway in CRC.An increased level of PACER enhances proliferation,migration,and invasion of tumor cells by increasing COX-2 and PGE2 synthesis.

麦门冬汤合苇茎汤加减治疗肺癌化疗患者的临床观察

目的:观察用麦门冬汤合苇茎汤加减治疗阴虚肺热证肺癌化疗患者的临床效果,探讨其可能的部分作用机制。方法:选取2017年6月至2018年6月滨州市中医医院收治的肺癌患者104例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组52例。对照组患者接受化疗干预,观察组患者在化疗干预的基础上给予麦门冬汤合苇茎汤加减方口服。观察近期疗效、患者生命质量、Th1/Th2细胞因子含量及外周血相关因子水平、不良反应的发生率。结果:观察组、对照组的近期疗效分别为65.38%、38.46%,以观察组近期疗效更好(P<0.05);治疗后,观察组患者的生命质量FACT-L评分均高于本组治疗前及对照组患者(P<0.05);对照组患者经化疗干预后免疫功能有所下降,而观察组患者免疫功能提高,外周血中Th1相关细胞因子IL-2、IFN-γ水平明显高于对照组,Th2相关细胞因子IL-4、IL-10水平明显低于对照组(P<0.05);观察组患者的血清中VEGF、COX-2、CYFRA21-1、CA19-9水平均显著低于对照组(P<0.05);观察组患者的不良反应较对照组明显减少(P<0.05)。结论:麦门冬汤合苇茎汤加减治疗阴虚肺热证肺癌化疗患者增效减毒作用明显,利于提高生命质量,其机制可能与纠正Th1/Th2细胞免疫失衡状态及抑制VEGF、COX-2表达而发挥抗血管增生作用有关。

Inhibitive Effect of Proanthocyanidins on Cyclooxygenase-2 Expression in A549 Cells Induced by Cytokine Interleukin-1 Beta

Cyclooxygenase-2(COX-2),an important enzyme,plays a pathological role in diseases,which can be inhibited by proanthocyanidins(PCs) effectively.In this paper,we investigated the inhibitive mechanism of COX-2 performed by PCs.Reverse transcription-polymerase chain reaction(RT-PCR) was performed to identify the mRNA expression level of COX-2 in A549 cell,which was induced by interleukin-1 beta(IL-1β).The pGL3 luciferase reporter vector containing the COX-2 gene promoter fragment(pGL3/COX-2p) was transfected into A549 cell induced by IL-1β,the interference on the COX-2 promoter activity from PCs was analyzed using a dualluciferase reporter assay,and the expressions of the nuclear factor κB composed of subunit p65(NF-κB/p65) and the inhibitor-κB(I-κB) were measured by the Western blotting and immunocytochemistry.The results exhibited that PCs not only inhibited the transcript of COX-2 mRNA and the COX-2 promoter activity,but also suppressed the nuclear translocation of NF-κB/p65 protein and the degradation of I-κB protein.

Effects of Manshenkangning Prescription on Adenine-induced Renal Interstitial Fibrosis in Rats

[Objectives]To study the protective effects of Manshenkangning Prescription on adenine-induced renal interstitial fibrosis in rats,and explore the possible mechanism.[Methods]Sixty Wistar male rats were divided into normal group,model group,control group(administered with 10 mg/(kg·d)losartan)and high,medium and low dose experimental groups(30,15,7.5 mg/(kg·d)Manshenkangning).The rat models of renal interstitial fibrosis were induced by intragastric administration of adenine(250 mg/(kg·d)).After 2 h,the above drugs were administered intragastrically for 21 consecutive days and the administration time was 30 consecutive days.Serum creatinine(SCr),blood urea nitrogen(BUN),24 h urinary protein(24 h MTP)and glomerular filtration rate(eGFR)were measured by biochemical method;renal histopathological changes were observed by hematoxylin-eosin(HE)staining.Renal collagen deposition in rats was observed by Masson staining.[Results]The SCr in model group and the high,medium and low dose experimental groups were(340.00±22.99),(176.80±18.60),(234.75±13.59),(266.11±14.78)μmol/L,and BUN were(23.74±2.51),(14.53±2.25),(18.78±0.88),(18.90±2.14)mmol/L;24 h MTP were(675.86±74.58),(323.81±41.83),(438.84±34.69),(493.76±37.04)mg/d;eGFR were(19.30±2.48),(49.96±10.95),(32.61±10.75),(27.18±5.98)mL/min,and the difference was statistically significant compared with the normal group(all P<0.05).HE staining and Masson staining showed that compared with normal group,the renal interstitial lesions in model group were severe and the renal interstitial collagen material was deposited in a large amount.The renal interstitial tubule injury was relieved and the renal interstitial collagen deposition was reduced in experimental groups.And the difference was statistically significant(all P<0.01).[Conclusions]Manshenkangning can significantly protect the kidney against the progress of interstitial fibrosis in rats.Its possible mechanism is to regulate the activity of SIRT1 and inhibit the expression of COX-2 in order to resist the inflammatory reaction of kidney and improve the ability of anti-oxidative stress of kidney,thus delaying the occurrence and development of chronic renal failure.