Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway

BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage(APD)attenuates intestinal mucosal injury in rats with severe acute pancreatitis(SAP),and improves administration of enteral nutrition in patients with acute pancreatitis(AP).However,the underlying mechanisms of the beneficial effects of APD remain poorly understood.AIM To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats,and its potential mechanisms.METHODS SAP was induced in male adult Sprague-Dawley rats by 5%sodium taurocholate.Mild AP was induced by intraperitoneal injections of cerulein(20μg/kg body weight,six consecutive injections).Following SAP induction,a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD.Morphological changes,serum inflammatory mediators,serum and ascites high mobility group box protein 1(HMGB1),intestinal barrier function indices,apoptosis and associated proteins,and toll-like receptor 4(TLR4)signaling molecules in intestinal tissue were assessed.RESULTS APD significantly alleviated intestinal mucosal injury induced by SAP,as demonstrated by decreased pathological scores,serum levels of D-lactate,diamine oxidase and endotoxin.APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells,and normalized the expression of apoptosis-associated proteins in intestinal tissues.APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1,thus exerting protective effects against SAP-associated intestinal injury.CONCLUSION APD improved intestinal barrier function,intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats.The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

Nuclear factor kappa B（NF-κB） in the spinal cord is involved in pro-infl ammatory cytokine-mediated pain facilitation. However, the role of NF-κB activation in chronic morphine-induced analgesic tolerance and the underlying mechanisms remain unclear. In the present study, we found that the level of phosphorylated NF-κB p65（p-p65） was increased in the dorsal horn of the lumbar 4–6 segments after intrathecal administration of morphine for 7 consecutive days, and the p-p65 was co-localized with neurons and astrocytes. The expression of TNF-α and IL-1β was also increased in the same area. In addition, pretreatment with pyrrolidinedithiocarbamate（PDTC） or SN50, inhibitors of NF-κB, prevented the development of morphine analgesic tolerance and alleviated morphine withdrawal-induced allodynia and hyperalgesia. The increase in TNF-α and IL-1β expression induced by chronic morphine exposure was also partially blocked by PDTC pretreatment. In another experiment, rats receiving PDTC or SN50 beginning on day 7 of morphine injection showed partial recovery of the anti-nociceptive effects of morphine and attenuation of the withdrawal-induced abnormal pain. Meanwhile, intrathecal pretreatment with lipopolysaccharide from Rhodobacter sphae-roides, an antagonist of toll-like receptor 4（TLR4）, blocked the activation of NF-κB, and prevented the development of morphine tolerance and withdrawal-induced abnormal pain. These data indicated that TLR4-mediated NF-κB activation in the spinal cord is involved in the development and maintenance of morphine analgesic tolerance and withdrawalinduced pain hypersensitivity.

桥本甲状腺炎合并甲状腺乳头状癌患者中Toll样受体3和核转录因子-κB的表达及相关性分析

目的分析桥本甲状腺炎(Hashimoto thyroiditis,HT)合并甲状腺乳头状癌(PTC)患者Toll样受体3(toll-like receptor 3,TLR3)和核转录因子-κB(nuclear transcription factor-κB,NF-κB)表达及相关性。方法收取邯郸市中心医院2020年3月~2022年3月收治的130例行手术切除的甲状腺标本,其中正常甲状腺组织标本43例,HT标本47例,HT合并PTC标本40例,分析TLR3和NF-κB在正常甲状腺组织、HT组、HT合并PTC组中的表达,分析HT合并PTC组中TLR3和NF-κB表达与临床病理参数关系,Pearson相关性分析TLR3和NF-κB的关系。结果TLR3在正常甲状腺组织、HT组、HT合并PTC组中的阳性表达率分别为0(0/43)、80.85%(38/47)、90.00%(36/40);NF-κB在以上三组中的阳性表达率分别为0(0/43)、68.09%(32/47)、85.00%(34/40)。TLR3和NF-κB在HT组、HT合并PTC组中的阳性表达率均高于正常甲状腺组织(P<0.05),TLR3和NF-κB表达与性别、年龄、HT合并PTC病理学特征、病灶类型、淋巴结转移、甲状腺包膜侵犯差异比较均无统计学意义(P均>0.05)。TLR3和NF-κB呈显著正相关(r=0.589,P<0.05)。结论TLR3和NF-κB在HT合并PTC组织中的阳性率高于正常甲状腺组织,且二者表达呈正相关。

Influence of Silencing TRAF6 with shRNA on LPS/TLR4 Signaling in vitro

This study investigated the influence of silencing TRAF6 with shRNA on lipopolysaccharide(LPS)/toll-like receptor(TLR)-4 signaling pathway in vitro.Four plasmids(pGCsi-TRAF6-shRNA1,2,3,4) containing different shRNA sequences were designed and synthesized.The proliferation of RAW264.7 cells after transfected with these plasmids was measured by MTT assay.Inflammatory cellular models were established by LPS stimulation.Levels of TNF-α,IL-1β and TGF-β1 in the supernatants,mRNA expressions of TRAF6,IL-6 and COX-2,protein expression of TRAF6 and translocation of NF-κB were assayed by ELISA,real-time quantitative PCR and Western blotting,respectively.The results showed that the TRAF6 gene knockdown by RNAi hardly inhibited the proliferation of RAW264.7 cells within 72 h.The mRNA and protein expression of TRAF6 was lower in the TRAF6-shRNA1,2 groups than in the TRAF6-shRNA3,4 groups.Therefore,pGCsi-TRAF6-shRNA1,2 were selected for the subsequent experiments.Our results still showed that pGCsi-TRAF6-shRNA1,2 could significantly reduce the production of pro-inflammatory cytokines and mediators including TNF-α,IL-1β,IL-6 and COX-2,and inhibit NF-κB nuclear translocation.Moreover,pGCsi-TRAF6-shRNA1,2 could suppress the release of TGF-β1 at the protein level.It was concluded that the recombinant plasmid pTRAF6-shRNA can,to some extent,inhibit inflammatory response stimulated by LPS at the initial phase.TRAF6 may become the potential therapeutic target of many inflammation-related diseases.

Role of Progesterone in TLR4-MyD88-dependent Signaling Pathway in Pre-eclampsia

The role of progesterone in the Toll-like receptor 4 （TLR4）-MyD88-dependent signaling pathway in pre-eclampsia was studied. Peripheral blood mononuclear cells （PBMCs） from pre-eclampsia （PE） patients were subjected to primary culture, and stimulated with different concentra- tions of progesterone （0, 10^-8, 10^-6, and 10^-4 mol/L）. The mRNA expression of TLR4, MyD88 and nu- clear factor-kappaB （NF-κB） was detected by using real-time PCR. The Ikappa-B protein expression was detected by using Western blotting. The expression of tumor necrosis factor-or （TNF-α and inter- leukin-6 （IL-6） in the supernatant was determined by using ELISA. With the concentrations of proges- terone increasing, the mRNA expression levels of TLR4, MyD88 and NF-κB in 2^△△CT value were sig- nificantly decreased, and the IkappaB protein expression levels were significantly increased. The TNF-α and IL-6 expression showed a downward trend when the progesterone concentration increased, and there were significant differences among all of the groups （P〈0.05）. It was suggested that progesterone can inhibit the TLR4-MyD88-dependent signaling pathway in PE significantly and benefit for the preg- nancy.

Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway

Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance.

穴位贴敷通过TLR4/MyD88/NF-κB通路调节原发性痛经大鼠的免疫功能

目的:基于Toll样受体(TLR)4/髓样分化因子(MyD)88/核转录因子κB p65(NF-κB p65)信号通路探讨石墨烯暖宫穴位贴对原发性痛经(PD)模型大鼠免疫功能的影响及对辅助性T淋巴细胞(Th)1/Th2免疫平衡的调节作用。方法:将SD雌性大鼠随机分成正常组、模型组和穴贴组,每组10只。股部皮下注射苯甲酸雌二醇制备PD模型。在造模的同时予穴贴组大鼠石墨烯暖宫穴位贴贴敷“关元”“子宫”(双侧)和“三阴交”(双侧)干预,连续10 d、1次/d、5 h/次。第11天腹腔注射缩宫素观察各组大鼠的扭体潜伏时间、30 min内的扭体次数,进行扭体评分;计算脾脏和胸腺的脏器指数;HE染色法观察大鼠脾脏和胸腺组织的病理变化;ELISA法检测血清免疫球蛋白(Ig)A、IgG、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-2、干扰素-γ(IFN-γ)、IL-4和IL-10含量;Western blot法和实时荧光定量PCR法分别检测大鼠子宫组织中TLR4、MyD88、NF-κB p65的蛋白及mRNA的相对表达量。结果:与正常组比较,模型组大鼠出现扭体反应(P<0.01),30 min内扭体次数和扭体评分显著增加(P<0.001);脾脏指数和胸腺指数均显著降低(P<0.01,P<0.05);脾脏和胸腺均出现了明显的病理变化;血清IgA、IgG、TNF-α、IL-2、IFN-γ含量显著升高,IL-4和IL-10含量显著降低(P<0.001,P<0.01);子宫组织TLR4、MyD88、NF-κB p65蛋白及mRNA表达均显著升高(P<0.001)。与模型组比较,穴贴组大鼠扭体潜伏时间延长(P<0.001),其他指标均逆转(P<0.001,P<0.01,P<0.05)。结论:石墨烯暖宫穴位贴可通过调控TLR4/MyD88/NF-κB p65信号通路,调节Th1/Th2的免疫平衡,修复免疫组织的病理损伤,改善免疫功能,从而有效缓解PD大鼠的疼痛症状。

多囊卵巢综合征伴胰岛素抵抗相关信号通路的研究进展

多囊卵巢综合征(PCOS)是一种好发于青春期及育龄期女性的涉及诸多因素的内分泌代谢性疾病,临床主要表现为闭经、体胖、多毛痤疮以及妊娠率显著降低,但目前其病因病机尚不清楚。胰岛素抵抗(IR)与多种慢性非传染性疾病(高血压、糖尿病、心脑血管疾病、PCOS等)相关,目前已知磷脂酰肌醇-3-激酶/蛋白激酶B、肝激酶B1/AMP活化的蛋白激酶、沉默信息调节因子1/叉头框转录因子O1、Toll样因子4/核因子κB信号通路参与了PCOS伴IR(PCOS-IR)的作用机制,因此充分认识PCOS-IR的发病机制在疾病预防中有重要临床意义。

Expression and signifi cance of TLR4 and HIF-1α in pancreatic ductal adenocarcinoma

AIM:To investigate the expression of toll-like receptor(TLR) 4,nuclear factor-κB(NF-κB) p65 and hypoxiainducible transcription factor 1α(HIF-1α) in pancreatic ductal adenocarcinoma and their clinical significance.METHODS:The mRNA of TLR4 and HIF-1α were investigated by real-time polymerase chain reaction in 30 cases of pancreatic ductal adenocarcinoma and its adjacent tissues,and expression of TLR4,NF-κB p65 and HIF-1α protein were detected by immunohistochemistry in 65 cases of pancreatic ductal adenocarcinoma tissues and 38 cases of corresponding adjacent tissues.The relationship between TLR4 or HIF-1α and pathologic features,as well as the association between TLR4 and HIF-1α,were also analyzed.Kaplan-Meier method was used to assess the impact of expression of TLR4 and HIF-1α on survival of patients with pancreatic cancer.RESULTS:The relative quantif ication of TLR4 and HIF-1α mRNA in tumor tissues was 0.81±0.10 and 0.87±0.11,respectively,signif icantly higher than that in adjacent tissues(0.81±0.10 vs 0.70±0.16,P=0.002;0.87±0.11 vs 0.68±0.13,P=0.000).The protein expression of TLR4,NF-κB p65 and HIF-1α in tumor tissues was 69.20%,66.15% and 70.80%,respectively,being signif icantly higher than that in adjacent normal tissues(69.20% vs 39.50%,P=0.003;66.15% vs 31.58%,P=0.001;70.80% vs 36.80%,P=0.001).There was no signif icant correlation between TLR4 or HIF-1α expression and the age,gender,tumor location,the degree of tumor differentiation in the patients(P>0.05).However,there was signif icant correlation between the expression of TLR4 or HIF-1α and tumor size,lymph node metastasis,venous invasion and clinical staging(P<0.05).The expression of TLR4 and HIF-1α had a signif icant impact on survival of patients with pancreatic adenocarcinoma.CONCLUSION:TLR4,NF-κB p65 and HIF-1α are overexpressed in pancreatic adenocarcinoma,TLR4 may be partly involved in up-regulating HIF-1α,and both synergestically promote development of pancreatic adenocarcinoma.

延胡索总碱贴片安全性和对神经病理性疼痛大鼠镇痛作用研究

目的 探讨延胡索总碱贴片的安全性及其对神经病理性疼痛大鼠的镇痛作用及其机制。方法 (1)安全性实验:采用单次、多次给药的皮肤刺激性实验及皮肤过敏性实验,评价延胡索总碱贴片的安全性。(2)镇痛实验:取48只雄性SD大鼠,随机分为正常组、假手术组、模型组、布洛芬组、双氯芬酸钠贴片组及延胡索总碱贴片高、中、低剂量组,每组6只。除正常组和假手术组外,其余组大鼠采用坐骨神经慢性压迫损伤方法诱导神经病理性疼痛模型,术后第8天开始,布洛芬组灌胃给药,双氯芬酸钠贴片组及延胡索总碱贴片高、中、低剂量组分别给予双氯芬酸钠贴片及延胡索总碱贴片腹部贴敷,其余组腹部贴敷空白贴片,均每天1次,连续14 d。分别于术前及干预后1,3,7,10,14 d测定各组大鼠热缩足反射潜伏期;采用Western blot法检测各组大鼠干预结束后脊髓中Toll样受体4(TLR4)、核因子κB(NF-κB)、p38丝裂原活化蛋白激酶(p38MAPK)、信号传导和转录激活因子3(STAT3)蛋白表达情况。结果 (1)给予延胡索总碱贴片后,皮肤刺激反应评分均小于0.5分,致敏率为0,组织结构与正常皮肤无差异。(2)镇痛实验中,延胡索总碱贴片中、高剂量组干预后3 d和延胡索总碱贴片各剂量组干预后7,10,14 d患侧的热缩足反射潜伏期均明显长于同期模型组(P均<0.05);干预结束后,延胡索总碱贴片各剂量组大鼠脊髓中TLR4、NF-κB、p38MAPK蛋白相对表达量均明显低于模型组(P均<0.05), STAT3蛋白相对表达量均明显高于模型组(P均<0.05)。结论 延胡索总碱贴片安全性良好,可抑制慢性坐骨神经挤压损伤神经病理性疼痛大鼠痛觉敏感,其机制可能与抑制脊髓中TLR4、NF-κB、p38MAPK表达并上调STAT3的表达有关。

Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency

The syndrome of dampness stagnancy due to spleen deficiency(DSSD)is relatively common globally.Although the pathogenesis of DSSD remains unclear,evidence has suggested that the gut microbiota might play a significant role.Radix Astragali,used as both medicine and food,exerts the effects of tonifying spleen and qi.Astragalus polysaccharide(APS)comprises a macromolecule substance extracted from the dried root of Radix Astragali,which has many pharmacological functions.However,whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown.Here,we used DSSD rats induced by high-fat and low-protein(HFLP)diet plus exhaustive swimming,and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes,decreased the levels of interleukin-1β(IL-1β),IL-6,and endotoxin,and suppressed the Toll-like receptor 4/nuclear factor-κB(TLR4/NF-κB)pathway.Moreover,a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size(LEfSe).APS increased the diversity of the gut microbiota and changed its composition,such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella,and increasing that of Parasutterella,Parabacteroides,Clostridium XIVb,Oscillibacter,Butyricicoccus,and Dorea.APS also elevated the contents of short-chain fatty acids(SCFAs).Furthermore,the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes.In general,our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota,especially for some bacteria involving immune and inflammatory response and SCFA production,as well as the TLR4/NF-κB pathway.This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.

Lipopolysaccharide-enhanced early proliferation of insulin secreting NIT-1 cell is associated with nuclear factor-kappaB- mediated inhibition of caspase 3 cleavage

Background Increased levels of plasma lipopolysaccharide （LPS） have been found in obesity and diabetes patients. This study was to investigate the effect of LPS on pancreatic beta-cell viability and the involvement of caspase 3 in NIT-1 cell line. Methods Mouse insulinoma NIT-1 cells were treated with LPS for the indicated time and dose. Cell viability was measured by cell counting kit-8 reagent. Toll-like receptor 4 （TLR4）, caspase 3 and cleaved caspase 3 were detected by Western blotting. Insulin was determined by radioimmunoassay （RIA）. Results LPS promoted NIT-1 cell proliferation at 1 μg/ml, peaked at 72 hours of incubation. A reduction in cleavage of caspase 3 was observed upon LPS treatment. Bay11-7082, a specific inhibitor of nuclear factor （NF）-κB, blunted LPS-induced inhibition of caspase 3 cleavage. Reduction in chronic insulin secretion was observed after treatment with LPS at 1 μg/ml for 48 and 72 hours, not for 24 hours. TLR4 protein was upregulated when NIT-1 cells were treated with LPS at 1 μg/ml for 24 hours. Conclusions LPS promotes early NIT-1 cell proliferation in association with NF-KB-mediated inhibition of caspase 3 cleavage. LPS exerts a time-dependent inhibitory effect on chronic insulin secretion from NIT-1 cells.

Therapeutic Effect of Crocin on Diabetic Retinopathy in Rats Based on TLR4/My D88/NF-κB Pathway

Objective:To study the therapeutic effect of crocin on diabetic retinopathy(DR)in rats based on toll-like receptor 4(TLR4)/myeloid differentiation factor 88(My D88)/nuclear factor-κB(NF-κB)pathway.Methods:Thirty SPF SD rats were used in the experiment,which were randomly divided into DR group,control group and crocin group,with 10 rats in each group.The DR rat model was established by feeding the rats in both the DR group and crocin group with a high glucose and high fat diet,along with intraperitoneal injection(IP)of streptozotocin.Crocin IP was administered to the rats in the crocin group,whereas the rats in the DR group and control group received an equivalent dosage of saline IP for 12 weeks.A comparison was made among the three groups regarding retinal thickness,vascular permeability,expression of TLR4/My D88/NF-κB pathway protein,levels of inflammatory factors,and levels of Bcl-2,Bax,and Bcl-2/Bax.Results:The DR group and crocins group exhibited a lower retinal thickness compared to the control group,while the crocins group displayed a higher thickness than the DR group.The DR group and crocins group had higher retinal vascular permeability than the control group,and the crocins group had lower retinal vascular permeability than the DR group(P<0.05).TLR4,My D88,and P-NF-κB relative expressions were higher in the DR and crocin groups than in the control group,whereas TLR4,My D88,and P-NF-κB relative expressions were lower in the crocin group than in the DR group(P<0.05).The DR group and crocin group exhibited elevated levels of inflammatory cytokines compared to the control group,while the crocin group displayed decreased levels in comparison to the DR group(P<0.05).The DR group and crocin group exhibited lower levels of Bcl-2 and Bcl-2/Bax compared to the control group,whereas the control group displayed higher levels of Bax.The crocin group exhibited elevated levels of Bcl-2 and Bcl-2/Bax compared to the DR group,whereas the DR group displayed diminished levels of Bax(P<0.05).Conclusion:Crocin has the potential to enhance the retinal thickness and vascular permeability of DR rats,and the inhibition of the TLR4/My D88/NF-κB pathway by crocin could play a crucial role in impeding the advancement of DR.

孕激素在子痫前期患者TLR4-MyD88依赖的信号通路中的作用

目的研究孕激素在子痫前期(preeclampsia,PE)孕妇Toll样受体4(toll-like receptor4,TLR4)-髓样细胞分化蛋白88(myeloid differentiation factor 88,My D88)依赖的信号通路中的作用。方法原代培养子痫前期孕妇外周血单个核细胞(peripheral blood mononuclear cell,PBMC),以不同浓度孕激素(0 mol/L、10-8mol/L、10-6mol/L、10-4mol/L)处理,实时定量聚合酶联反应(Real-time polymerase Chain reaction,real-time PCR)检测TLR4 mRNA、My D88 mRNA、核转录因子-κB(nuclear factorκB,NF-κB)mRNA的表达;免疫印迹法Western blot检测IκB-α蛋白的表达,用凝胶图像处理系统分析各条目标带灰度值酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)检测细胞上清液中肿瘤坏死因子-α(tumor necrosis factors,TNF-α)及白介素-6(interleukin-6,IL-6)的表达。结果随着孕酮浓度的增加,各组TLR4 mRNA、My D88mRNA及NF-κB mRNA的相对表达量2-△△Ct均逐渐降低,IκB-α蛋白的表达逐渐增加,差异均有统计学意义(均P<0.05);同时,细胞上清液中细胞因子TNF-α及IL-6的表达均逐渐减少,差异均有统计学意义(P<0.05)。结论孕激素可显著抑制TLR4-My D88依赖的信号传导通路,对子痫前期患者具有保护作用。