子宫内膜异位症在位内膜MUC1与TNFR-I表达的关系

目的检测子宫内膜异位症(EMs)患者在位内膜黏蛋白1(MUC1)和肿瘤坏死因子受体I(TNFR-I)的表达,探讨血清中肿瘤坏死因子(TNF-α)含量的调控机制及与EMs性不孕的内在联系。方法采集28例EMs患者(EMs组)及26例输卵管因素不孕患者(对照组)的在位子宫内膜,采用IHC方法检测内膜MUC1的表达,Western blot法检测TNFR-I的表达;用ELISA法检测血清TNF-α水平。结果 EMs在位内膜MUC1在不同月经周期的表达差异不明显,其在分泌中期的表达量较对照组明显减少。EMs组血清TNF-α含量显著高于对照组;而TNFR-I表达则低于对照组。结论 EMs在位内膜MUC1表达的改变,可能是EMs性不孕的原因之一;TNF-α缺乏促进在位内膜MUC1表达的作用可能与TNFR-I的低表达有关。     

子宫内膜异位症异位和在位内膜中水通道蛋白1的表达及意义探讨

目的探讨子宫内膜异位症异位和在位内膜中水通道蛋白1的表达及意义。方法以2011年10月至2012年12月我院收治的子宫内膜异位症患者39例为观察对象,对患者异位内膜和在位内膜测量水通道蛋白1。并以同期收治的子宫内膜正常组为对照组。观察三组标本的检查结果。结果正常健康组被检者的水通道蛋白1值最低,组间比较,P<0.05;子宫内膜异位症组异位内膜的水通道蛋白1与在位内膜比较有显著差异,P<0.05。结论子宫内膜异位症患者的水通道蛋白1较高,可能参与到疾病的发生和发展中。     

子宫内膜异位症患者异位内膜组织中基质金属蛋白酶表达及其意义

目的 研究基质金属蛋白酶（MMP-1、MMP-9）在子宫内膜异位症发生中的作用。方法 采用免疫组化方法研究40例子宫内膜异位症患者的病理组织和32例正常子宫内膜组织中的MMP-1、MMP-9的表达情况。结果 子宫内膜异位症患者病理组织中MMP-1、MMP-9的表达水平明显高于对照组（P〈0．01）。结论 MMP-1、MMP-9在子宫内膜异位症发生中起一定的作用。     

KISS-1在子宫内膜异位症患者异位内膜中的表达及意义

目的 了解KISS-1在正常子宫内膜及子宫内膜异位症患者异位内膜组织中的表达关系.方法 采用免疫组织化学EliVision plus技术,检测46例患者异位子宫内膜组织,55例正常子宫内膜组织中KISS-1的表达情况,对两组间表达情况进行比较.结果 KISS-1在子宫内膜异位症患者异位内膜及正常子宫内膜组织中阳性表达率分别为30.43%和63.64%,差异有统计学意义(P<0.01,P<0.05).结论 KISS-1在子宫内膜异位症中的表达减弱可能与内异症的发病有关.     

子宫内膜异位症患者在位子宫内膜Fas、FasL的表达及其意义

目的检测子宫内膜异位症患者在位子宫内膜Fas及其配体(FasL)的表达,探讨其在子宫内膜异位症发生机制中的作用.方法采用免疫组织化学法(SP法)对45例盆腔子宫内膜异位症和44例壁间型子宫肌瘤患者在位子宫内膜进行Fas、FasL表达检测.结果(1)对照组Fas、FasL主要表达于子宫内膜腺上皮细胞胞浆和/或胞膜.增生期Fas、FasL表达显著低于分泌期(P＜0.05).(2)子宫内膜异位症组Fas、FasL亦主要表达于子宫内膜腺上皮细胞胞浆和/或胞膜.增生期与分泌期Fas、FasL表达差异无显著意义.(3)与对照组比较,子宫内膜异位症组分泌期Fas、FasL表达显著低于对照组(P＜0.05).结论子宫内膜周期性生理变化与Fas及其配体的表达水平改变有关.子宫内膜异位症在位子宫内膜分泌期凋亡敏感性降低.推测这种具有抗凋亡活性的子宫内膜细胞逆流至盆腹腔后,因其Fas低水平表达,得以逃避机体免疫清除系统的影响而在异位存活、种植,为子宫内膜异位症的发生创造了先决条件.     

MMP-9在子宫内膜异位症患者异位及在位内膜的表达及意义

目的探讨MMP-9在子宫内膜异位症患者异位及在位内膜组织的表达及意义。方法用免疫组化方法检测40例患者异位子宫内膜组织及其中25例在位内膜组织和15例正常子宫内膜组织中MMP-9的表达情况。结果 MMP-9表达率分别为82.5%（33/40）、48%（12/25）,33.3%（5/15）,差异有统计学意义（P〈0.05）。结论 MMP-9的表达增高可能与内异症的侵袭有关。     

子宫内膜异位症患者在位内膜和异位内膜中的Bim和p21 WAF1/CIP1表达及相关性研究

目的探讨Bim和p21 WAF1/CIP1在子宫内膜异位症发病中的作用及相关性。方法采用免疫组化SP法检测30例正常子宫内膜和30例子宫内膜异位症患者的在位内膜和异位内膜的Bim和p21 WAF1/CIP1的表达。结果Bim在正常子宫内膜、子宫内膜异位症的在位内膜、异位内膜的表达分别为86.7%、60%、43.3%,p21 WAF1/CIP1在子宫内膜异位症的在位内膜、异位内膜的表达分别为83.3%、56.7%、46.7%。子宫内膜异位症的在位内膜组、异位内膜组中,Bim和p21 WAF1/CIP1均呈正相关。结论Bim和p21 WAF1/CIP1的凋亡与增殖作用在子宫内膜异位症的发展中起相互促进作用。     

子宫内膜异位症痛经患者内膜组织中雌激素受体表达的相关研究

目的 检测内异症痛经患者内膜组织中雌激素受体的表达,分析其与疼痛及其程度的关系.方法 内异症组50例,其中在位内膜组40例,异位内膜组10例,对照组30例,在位内膜组患者术前均对痛经程度进行评分,采用免疫组化法测定雌激素受体的表达.结果 EMs组在位内膜ER蛋白的表达高于对照组,差异有显著性(P＜0.05);EMs疼痛组与无痛组的表达差异有显著性(P＜0.05);ER蛋白在EMs重度疼痛组组织中阳性灰度值最高,而在轻度疼痛组灰度值最低,三组间比较差异均有显著性(P＜0.05).结论 内异症病灶局部雌激素受体表达增加,可能与子宫内膜异位症疼痛的发生、发展密切相关.     

基于在位和异位内膜Bcl-w蛋白表达的子宫内膜异位症机制探讨

目的 探讨凋亡抑制基因Bcl-w在子宫内膜异位症的发生发展中的作用.方法 采用免疫组织化学染色法(SP法)检测凋亡抑制基因Bcl-w分别在正常子宫内膜组织、子宫内膜异位症患者的异位内膜组织和在位内膜组织中的表达水平.结果 Bcl-w在子宫内膜的腺上皮细胞和间质细胞中均有表达,以腺上皮细胞浆中表达明显,偶有细胞膜和细胞核表达.异位子宫内膜组和在位子宫内膜组Bcl-w的表达高于正常子宫内膜组,差异有统计学意义(均P＜ 0.01);Bcl-w在异位子宫内膜组的表达高于在位子宫内膜组,差异有统计学意义(P＜0.05).结论 凋亡抑制基因Bcl-w在子宫内膜异位症的发生发展中起着很重要的作用.     

SIRT1、SIRT2和IL-37在子宫内膜异位症患者异位内膜组织的表达

目的 探讨 Sirtuin1（SIRT1）、Sirtuin2（SIRT2）及白细胞介素-37（IL-37）在正常子宫内膜组织及异位子宫 内膜组织表达的差异。方法 收集正常人子宫内膜组织及异位症患者异位内膜组织各 30例,采用免疫组织化学染 色检测 SIRT1、SIRT2及 IL-37蛋白的表达情况。结果 子宫内膜异位症患者异位内膜组织中 SIRT1、SIRT2、IL-37的 阳性表达率分别为 33.0%、20.0%、36.7%,均较正常子宫内膜组织（分别为 90.0%、86.7%、86.7%）显著降低（P＜0.05）。 不同月经周期对子宫内膜 SIRT1、SIRT2及 IL-37的表达无明显影响（P＞0.05）。结论 子宫内膜异位症患者异位内 膜中 SIRT1、SIRT2及 IL-37表达水平较低,提示子宫内膜异位症患者的异位内膜组织可能存在炎症反应。     

血清炎性生物标记物在子宫内膜异位症患者血清中的表达及意义

目的：探讨炎性因子TNF－α、IL－1β、IL－6、IL－8及CA－125、MMP－3、VEGF在子宫内膜异位症患者血清中表达变化及其意义,分析其与患者EMs病变r－AFS临床分期及EMs患者痛经程度的相关性。方法采用酶联免疫法（ELISA）检测入组患者血清中TNF－α、IL－1β、IL－6、 IL－8,CA－125、MMP－3、VEGF的浓度。分析EMs患者血清中TNF－α、IL－1β、IL－6、IL－8、CA－125、MMP－3、VEGF的浓度与正常对照人群的差异;分析不同分期EMs患者血清中上述标记物的浓度差异;分析EMs患者术前术后血清中上述标记物的表达变化情况;分析EMs患者血清中上述标记物与痛经评分的相关性。结果炎性相关因子TNF－α、IL－1β、IL－6、IL－8及CA－125、VEGF浓度在EMs患者血清中显著升高（ P ＜0．05）,并且随着EMs病变γ－AFS临床分期加重而增加,手术切除病灶后血清中上述指标浓度迅速回落;此外严重痛经EMs患者血清中TNF－α、IL－1β及IL－6的浓度较无痛经EMs患者高（ P ＜0．05）。 EMs患者血清中TNF－α、IL－1β及IL－6浓度与患者痛经严重程度呈正相关（ P ＜0．05）。 MMP3－在EMs患者血清中浓度显著升高（ P ＜0．05）,手术切除病灶后血清中MMP－3迅速下降,然而血清中MMP－3浓度与EMs患者r－AFS临床分期无显著性关联,血清中MMP－3浓度与EMs患者痛经严重程度亦无明显相关性（ P ＜0．05）。结论测定EMs患者血清中TNF－α、IL－1β、IL－6、IL－8及CA－125、MMP3－、VEGF浓度对于EMs的临床诊断具有一定价值,并且可作为无创性辅助检查手段。     

Interactions between CB(1) receptors and TRPV1 channels mediated by 12-HPETE are cytotoxic to mesencephalic dopaminergic neurons

Background and purposes:We recently proposed the existence of neurotoxic interactions between the cannabinoid type 1 (CB(1)) receptor and transient receptor potential vanilloid 1 (TRPV1) channels in rat mesencephalic cultures. This study seeks evidence for the mediator(s) and mechanisms underlying the neurotoxic interactions between CB(1) receptors and TRPV1 in vitro and in vivo.Experimental approach:The mediator(s) and mechanism(s) for the interactions between CB(1) receptors and TRPV1 were evaluated by cell viability assays, immunocytochemistry, Fura-2 calcium imaging, mitochondrial morphology assay, ELISA and Western blot assay in vitro in neuron-enriched mesencephalic cultures. Injections into the substantia nigra and subsequent cell counts were also used to confirm these interactions in vivo.Key results:The neurotoxic interactions were mediated by 12(S)-hydroperoxyeicosatetraenoic acid (12(S)-HPETE), an endogenous TRPV1 agonist. CB(1) receptor agonists (HU210 and WIN55,212-2) increased the level of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a downstream metabolite of 12(S)-HPETE, which stimulates TRPV1-mediated death of mesencephalic neurons, both in vitro and in vivo. The neurotoxicity was mediated by increased intracellular Ca(2+) concentration ([Ca(2+)](i)) through TRPV1, consequently leading to mitochondrial damage and was attenuated by baicalein, a 12-lipoxygenase inhibitor.Conclusion and implications:Activation of CB(1) receptors in rat mesencephalic neurons was associated with biosynthesis of 12(S)-HPETE, which in turn stimulated TRPV1 activity, leading to increased [Ca(2+)](i), mitochondrial damage and neuronal death.British Journal of Pharmacology (2008) 155, 253-264; doi:10.1038/bjp.2008.246; published online 16 June 2008.     

子宫内膜异位蛋白质(ENDO-1)在内异症组织的表达及其临床意义

目的 探讨子宫内膜异位蛋白质(END0—1)在子宫内膜异位症内的表达及其意义。方法采用逆转录一多聚合酶反应(RT—PCR)方法检测两组组织中子宫内膜异位蛋白质(END0-1)的阳性表达情况。研究组为20例配对的内异症患者(异位灶及在位内膜)，对照组为15例无异位症患者的在位内膜。结果研究组20例显示：在内异症的异住病灶内这种物质在黄体期内的表达有明显的差异性(P=0．004)。研究组患者黄体期的在位内膜与对照组相比，后者表达水平较低(P=0．04)，差异有显著性。结论因此END0-1在诊断内异位方面可能是一个特异性的标志物，对异位症的发病机制方面，尤其是免疫机理，可以对之作出较好的解释，同时也为内异症的治疗提供一个新的方向。     

Possible involvement of the transient receptor potential vanilloid type 1 channel in postoperative adhesive obstruction and its prevention by a kampo (traditional Japanese) medicine, daikenchuto

This study focused on the localization of transient receptor potential vanilloid type 1 (TRPV1) in the intestines in postoperative adhesion model rats and investigated the underlying mechanism for the anti-adhesion action of daikenchuto (DKT), especially in relation to TRPV1. Postoperative intestinal adhesion was induced by sprinkling talc in the small intestine. The expression of TRPV1 mRNA was examined by in situ hybridization and real-time RT-PCR. The effects of DKT and its major ingredient, hydroxy sanshool, with or without ruthenium red, a TRP-channel antagonist, on talc-induced intestinal adhesions were evaluated. The level of TRPV1 mRNA was higher in the adhesion regions of talc-treated rats than in normal small intestine of sham-operated rats. Localization of TRPV1 mRNA expression was identified in the submucosal plexus of both sham-operated and talc-treated rats; and in talc-treated rats, it was observed also in the myenteric plexus and regions of adhesion. Capsaicin, DKT, and hydroxy sanshool significantly prevented formation of intestinal adhesions. The effects of DKT and hydroxy sanshool were abrogated by subcutaneous injection of ruthenium red. These results suggest that pharmacological modulation of TRPV1 might be a possible therapeutic option in postoperative intestinal adhesion, which might be relevant to the prevention of postoperative adhesive obstruction by DKT.     

Phosphorylation of TRPV1 by neurokinin-1 receptor agonist exaggerates the capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons

The present study was conducted to determine whether the activation of neurokinin-1 receptor (NK-1R) by its agonist (GR73632) enhances the capsaicin-evoked substance P (SP) release using a radioimmunoassay. A pre-exposure to GR73632 enhanced the capsaicin-evoked SP release in a time- and dose-dependent manner. The augmentation of capsaicin-evoked SP release by GR73632 was completely inhibited by pharmacological blockade of NK-1R or transient receptor potential vanilloid receptor subtype 1 (TRPV1), and was partially attenuated by the inhibition of either protein kinase C (PKC), cyclooxygenase (COX) or phospholipase C (PLC), p38 or p42/44 mitogen-activated protein (MAP) kinase, but not protein kinase A. This augmentation of SP release was further increased by inhibition of c-Jun NH2-terminal kinase. A short-term (10min) exposure to GR73632 resulted in an increase in the TRPV1 phosphorylation. The increase in the TRPV1 phosphorylated forms induced by a 60-min exposure to GR73632 was completely abolished by the inhibition of either PKC, COX or PLC, p38 or p42/44 MAP kinases. Immunocytochemistry study demonstrated that the NK-1R and TRPV1 were mainly co-expressed in the small-sized neurons. These findings suggest that the activation of NK-1R by its agonist, by sensitizing the TRPV1 through the PKC phosphorylation of TRPV1, may play a role in the enhancement of the capsaicin-evoked SP release from cultured rat DRG neurons.     

Effects of SA13353, a Transient Receptor Potential Vanilloid 1 Agonist,on Leukocyte Infiltration in Lipopolysaccharide-Induced Acute Lung Injury and Ovalbumin-Induced Allergic Airway Inflammation

We recently demonstrated that SA13353, a transient receptor potential vanilloid 1 (TRPV1) agonist, reduced the severity of the symptoms of kidney injury, arthritis, and encephalomyelitis in disease models. Here, we investigated the effects of orally administered SA13353 on leukocyte infiltration in lipopolysaccharide (LPS)-induced acute lung injury and ovalbumin-induced allergic airway inflammation. In LPS-induced lung injury, SA13353 attenuated neutrophil infiltration and the increase of TNF-α and CINC-1 levels. In allergic airway inflammation, SA13353 tended to inhibit leukocyte infiltration and attenuated the increase of IL-4 and IL-12p40. These results suggest that somatosensory TRPV1 may play an anti-inflammatory role in lung inflammation.