Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates inflammatory response ulcerative colitis through TLR4/NF-κB signaling pathway

BACKGROUND Ulcer colitis(UC)is a chronic,nonspecific,and noninfectious inflammatory bowel disease.Recently,Toll-like receptors(TLRs)have been found to be closely associated with clinical inflammatory diseases.Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging.Moreover,no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.AIM To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.METHODS This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021.The patients with UC were divided into two groups(control and experimental).The peripheral blood of the experimental and control groups were collected under aseptic conditions.The expression of TLR4 protein,NF-κB,IL-6,and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug.Linear co rrelation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17,and P<0.05 was considered statistically significant.RESULTS There were no significant differences in the patient characteristics between the control and experimental groups.The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group(P<0.05).The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group(P<0.05).The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17(r=0.823,P<0.05).CONCLUSION Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.

Effect of dexmedetomidine on the prevention of PSH in patients with severe craniocerebral injury by regulating TLR4/My D88/NF-kappa B signaling pathway

Objective:To investigate the clinical efficacy of dexmedetomidine in the regulation of TLR4/My D88/NF-κB in the prevention of paroxysmal sympathetic over-excitation (PSH) in patients with severe head injury. Methods:One hundred patients with severe head injury who were admitted to our hospital from September 2016 to May 2019 were enrolled. The randomized digital table method was divided into 50 cases in the study group and the control group. Patients in the study group were given dexmedetomidine at a dose of 1.0 μg/kg before anesthesia induction, followed by infusion at 0.4 μg / (kg·h), and the control group was injected with the same amount of normal saline. The incidence of PSH, clinical symptoms, imaging findings, mechanical ventilation time, tracheal intubation/incision duration, ICU hospitalization time, total length of hospital stay, and GCS scores three months after discharge were compared between the two groups. At the same time, the fluorescence intensity, TLR4, NF-κB expression level and tumor necrosis factor-α (TNF-α) expression levels in peripheral blood CD14+ monocytes of the two groups were detected. Results:The incidence of PSH was significantly lower in the study group than in the control group at 7 and 3 months (P<0.05). The total length of hospital stay, duration of ICU hospitalization, intraoperative tracheotomy, and mechanical ventilation time were significantly lower in the study group than in the control group. And the GCS score was higher than the control group, and the difference was statistically significant (P<0.05). In addition, the imaging results showed that there were some differences in the location of imaging lesions between the two groups. The proportion of lesions in the ventricular system and surrounding areas was higher in the control group than in the study group (P<0.05). And the T14-T3 CD14+ PBMC MyD88 fluorescence intensity, TLR4 and NK-κB positive expression rate were significantly higher than those of T0 (P<0.05), but the MyD88 fluorescence intensity, TLR4 and NK-κB positive expression rate in the study group were significantly lower than those in the control group at T1~T3 (P<0.05). The levels of serum TNF-α in T1~T3 groups were significantly higher than those in T0 (P<0.05), but the levels of serum TNF-α in T1~T3 in the study group were significantly lower than those in the control group (P< 0.05). Conclusions:Dexmedetomidine can reduce the oxidative stress response in patients with severe head injury by inhibiting TLR4/My D88/NF-κB signaling pathway, thus effectively reducing the risk of PSH and improving the prognosis of patients.

β-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation in mice

AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway.RESULTS Compared with wild-type mice, the β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of proinflammatory cytokines, including interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines(including IL-1β, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the β-arrestin 2 si RNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phosphoIκBα and phosho-p65, were upregulated.CONCLUSION β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation.

右归丸对肾阳虚证患者TLR4/MyD88/NF-κB信号通路表达的影响

目的探讨右归丸治疗肾阳虚证的免疫调控机制。方法筛选9例肾阳虚证患者,均给予右归丸口服,连服1个月。分别于治疗前后采集患者外周静脉血,制备外周血单个核细胞(PBMC),提取RNA,按照实时定量PCR(q PCR)实验流程,检测TLR4、My D88及NF-κBmRNA表达情况,并进行比较分析。结果治疗后,患者TLR4mRNA表达水平明显下调(P<0.05),My D88、NF-κB mRNA表达水平均明显上调(P均<0.05)。结论右归丸可以调节TLR4/My D88/NF-κB信号通路的表达,这可能是右归丸良性调节肾阳虚证免疫功能的分子机制之一。

安子合剂对抗磷脂抗体阳性流产小鼠TLR4/MyD88/NF-κB信号通路的影响

目的:研究安子合剂对抗磷脂抗体(APA)阳性流产小鼠Toll样受体4(TLR4)/髓样分化因子88(My D88)/核因子κB(NF-κB)信号通路的影响,探讨其抗APA阳性流产作用机制。方法:将BALB/c小鼠(♀)随机分为空白对照组、模型组、阿司匹林组(阳性对照,0.019 5 g/kg)和安子合剂低、中、高剂量组(37.7、75.4、150.8 g/kg,以生药计),每组10只。除空白对照组外,其余各组小鼠均以人β2-糖蛋白Ⅰ为诱导剂建立APA阳性流产模型。从妊娠第1天起,各给药组小鼠ig相应药物,空白对照组和模型组小鼠ig等体积生理盐水,每天1次,连续9 d。分别采用实时荧光定量聚合酶链反应法和免疫组化法测定胎盘组织TLR4、髓样分化蛋白2(MD2)、My D88、NF-κB m RNA及其蛋白表达水平。结果:与空白对照组比较,模型组小鼠胎盘组织TLR4、MD2、My D88、NF-κB m RNA及其蛋白表达水平均显著升高(P<0.01)。与模型组比较,阿司匹林组和安子合剂低、中剂量组小鼠胎盘组织TLR4、MD2、My D88 m RNA及其蛋白表达水平,安子合剂高剂量组小鼠胎盘组织TLR4蛋白表达水平,以及各给药组小鼠胎盘组织NF-κB蛋白表达水平均显著降低(P<0.05或P<0.01);安子合剂低剂量组小鼠胎盘组织TLR4、MD2 m RNA表达水平和MD2、My D88蛋白表达水平较阿司匹林组更低(P<0.05或P<0.01)。结论:安子合剂可抑制APA阳性流产小鼠TLR4/My D88/NF-κB信号通路转导,这可能是其抗APA阳性流产的作用机制之一。

青藤碱对类风湿关节炎患者外周血单核细胞TLR4、MyD88及NF-κB表达的影响

目的:观察青藤碱(SN)对脂多糖(LPS)诱导的类风湿关节炎(RA)患者外周血单核细胞TLR4/My D88/NF-κB m RNA及蛋白表达的影响。方法:采用活动期RA患者外周血进行单核细胞的分离培养,并与健康志愿者做对照。分为健康对照组、RA对照组、RA+LPS组,SN低剂量组,SN高剂量组及TAK-242组进行观察。采用RT-PCR法及Western blot法检测各组TLR4、My D88及NF-κB m RNA及蛋白的表达。结果:RA对照组TLR4、My D88及NF-κB m RNA及蛋白表达均明显高于健康对照组(P<0.01);RA+LPS组均明显高于RA对照组(P<0.01);SN低剂量组、SN高剂量组均明显低于RA+LPS组(P<0.01),且SN不同剂量组之间差异有统计学意义(P<0.01)。结论:SN可有效抑制LPS诱导的单核细胞TLR4、My D88及NF-κBm RNA及蛋白的表达,其对RA的治疗作用可能与抑制TLR4/My D88/NF-κB信号通路介导的炎症反应有关。

Bioinformatic Analysis and Experimental Verification of QJHGD on Caerulein-induced Inflammatory Response in SAP Model Rats Based on TLR4/NF-κB/My D88 Pathway

[Objectives]To conduct bioinformatic analysis and experimental verification of Qingjie Huagong Decoction(QJHGD)on caerulein-induced inflammatory response in severe acute pancreatitis(SAP)model rats based on TLR4/NF-κB/MyD88 pathway.[Methods]The effective component groups and potential targets of QJHGD were collected by the network pharmacology method.A drug-component-target network was constructed.The GO and KEGG of targets were enriched and analyzed with the aid of Metascape database,and the target pathway related to SAP inflammation was screened.The SAP rat model was established by caerulein combined with lipopolysaccharide,and QJHGD was intragastrically administered.Pancreatic tissue was observed by HE staining.In addition,enzyme-linked immunosorbent assay and immunohistochemistry were used to verify the anti-inflammatory effect of QJHGD on SAP rats and its regulatory effect on TLR4/NF-κB/MyD88 target pathway.[Results]A total of 105 active components of QJHGD and 148 key targets of SAP were predicted and screened;KEGG was enriched in 320 different pathways including toll-like receptor and NF-κB classical pathways.Animal experiment verified that QJHGD reduced serum amylase,serum lipase activity,IL-6,TNF-αlevels in SAP rats;HE staining showed the effect of QJHGD on the pathological changes of pancreas,and QJHGD inhibited the positive expression of key proteins of TLR4,NF-κB and MyD88 in the inflammatory transduction pathway.[Conclusions]The mechanism of QJHGD improving pancreatic injury in SAP rats may be related to down-regulating the expression of key proteins in the TLR4/NF-κB/MyD88 pathway.

化合物W3D通过调控TLR4-MyD88-NF-κB通路抑制LPS诱导的RAW264.7细胞炎症因子的释放

目的建立脂多糖(LPS)诱导的小鼠单核巨噬细胞(RAW264.7)炎症模型,探究新型苯并噁唑酮衍生物4-(5'-二甲氨基)-萘磺酰氧基苯并噁唑酮(W3D)的抗炎活性及其对TLR4-MyD88-NF-κB通路的调控作用。方法 MTT法测定化合物W3D对细胞活力的影响;LPS与不同浓度的化合物W3D共同作用RAW264.7细胞后,ELISA法测定细胞上清液中TNF-α、IL-6、IL-1β、COX-2的含量,Western blot法检测IL-6、TLR4、MyD88、IRAK4、NF-κB的蛋白表达;实时荧光定量PCR法检测细胞中TLR4、MyD88、IL-6 mRNA的表达。结果化合物W3D对LPS诱导的RAW264.7细胞培养液中炎症因子TNF-α、IL-6、IL-1β的分泌有明显的抑制作用,但对COX-2无抑制活性;可明显下调TLR4、MyD88、IL-6的蛋白与mRNA的表达,抑制IRAK4磷酸化和NF-κB的入核活化。结论化合物W3D可通过调控TLR4-MyD88-IRAK4-NF-κB信号通路,抑制TNF-α、IL-6、IL-1β等炎症因子的释放而发挥抗炎活性。

右美托咪定通过调控TLR4/My D88/NF-κB信号通路预防重型颅脑损伤患者PSH的疗效观察

目的探讨右美托咪定调控Toll样受体4(TLR4)/髓样分化因子(MyD)88/核转录因子(NF)-κB信号通路(TLR4/My D88/NF-κB)预防重型颅脑损伤患者阵发性交感神经过度兴奋(paroxysmal sympathetic hyperactivity,PSH)的临床疗效。方法选取本院2016年9月~2019年5月收治的100例重型颅脑损伤患者为研究对象,随机数字表法分为研究组和对照组各50例,研究组在麻醉诱导前给予1.0μg/kg负荷量的右美托咪定,后续以0.4μg·kg-1·h-1输注,对照组注射等量生理盐水。比较两组PSH发生率、临床症状、影像学表现、机械通气时间、气管插管/切开时长、ICU住院时间、总住院时长以及出院后3个月的GCS评分;同时检测两组治疗后外周血CD14+单核细胞中MyD88的荧光强度、TLR4、NF-κB表达水平,以及肿瘤坏死因子-α(TNF-α)表达水平。结果研究组7 d和3个月时PSH发生率显著低于对照组(P<0.05),且研究组总住院时长、ICU住院时长、术中气管切开比例以及机械通气时间均显著低于对照组,GCS评分高于对照组,差异具有统计学意义(P<0.05)。另外影像学结果显示两组患者的影像学病灶位置存在一定差异,对照组中患者病灶位于脑室系统及周围的比例高于研究组(P<0.05)。两组T1~T3时CD14+PBMC MyD88荧光强度、TLR4和NK-κB阳性表达率相比T0均显著增高(P<0.05),但研究组患者在T1~T3时MyD88荧光强度、TLR4和NK-κB阳性表达率相比对照组明显降低(P<0.05)。两组T1~T3时血清TNF-α表达水平相比T0均显著增高(P<0.05),但研究组T1~T3时血清TNF-α表达水平相比对照组明显降低(P<0.05)。结论右美托咪定可以通过抑制TLR4/My D88/NF-κB信号通路减少重型颅脑损伤患者机体氧化应激反应,从而有效降低PSH发生风险,改善患者预后。

Blautia producta displays potential probiotic properties against dextran sulfate sodium-induced colitis in mice

Blautia has attracted attention because of its potential efficacy in ameliorating host energy metabolism and inflammation.This study aims to investigate the influences of Blautia producta D4 on colitis induced by dextran sulfate sodium(DSS)and to reveal the underlying mechanisms.Results showed that B.producta D4 intervention significantly relieved body weight loss,and suppressed the elevation of pro-inflammatory cytokines(including interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β))and excessive oxidative stress(myeloperoxidease(MPO)activity,superoxide dismutase(SOD)activity,glutathione peroxidase(GSH-Px)activity,and malondialdehyde(MDA)level)in colitis mice.Moreover,the concentrations of tight junction proteins(occludin,claudin-1,and ZO-1)related to the intestinal barrier were obviously elevated,and colitis-related TLR4/NF-κB pathway activation was remarkably inhibited after B.producta D4 intervention.The intestinal microbial disorder was evidently ameliorated by increasing the relative abundance of Clostridium sensu stricto 1,Bifidobacterium,GCA-900066225,Enterorhabdus,and reducing the relative abundance of Lachnospiraceae NK4A136 group.In conclusion,oral administration of B.producta D4 could ameliorate DSS-induced colitis by suppressing inflammatory responses,maintaining the intestinal barrier,inhibiting TLR4/NF-κB pathway,and regulating intestinal microbiota balance.These results are conducive to accelerate the development of B.producta D4 as a functional probiotic for colitis.

布地奈德混悬液对哮喘模型小鼠肺组织TLR4/MyD88/NF-κB通路的影响

目的:探究布地奈德混悬液对哮喘模型小鼠肺组织TOLL样受体4(toll-like receptor 4,TLR4)/髓样分化因子88(myeloid differentiation factor 88,My D88)/核因子κB(nuclear factor-κB,,NF-κB)通路的影响。方法:使用4%鸡蛋清白蛋白与2%的Al(OH3)共同致敏小鼠,建立咳嗽变异性哮喘小鼠模型40只,将模型大鼠分别使用低、中、高剂量(0.2、1.0、2.0 g/kg)布地奈德混悬液和孟鲁司特钠进行干预,1次/日连续干预14 d,于干预14 d时采集小鼠的支气管肺泡灌注液(bronchoalveolar lavage fluid,BALF)、气管及肺组织,对各组BALF中的白细胞(white blood cell,WBC)、嗜酸性粒细胞、血清γ干扰素(interferon-γ,IFN-γ)、白细胞介素-1β(interleukin-1β,Il-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平差异开展比较,对各组小鼠肺组织黏膜上皮增生程度评分、炎症细胞浸润程度评分、病变总评分差异,以及TLR4、My D88、p65蛋白表达差异进行分析。结果:分析显示,布地奈德混悬液能够显著降低哮喘模型小鼠BALF中白细胞及嗜酸性粒细胞数量,同时还能够改善小鼠气管和支气管黏膜上皮增生与肺组织炎症细胞浸润状态,且干预后小鼠肺组织中的TLR4、My D88、p65蛋白表达水平出现了明显的降低。结论:布地奈德混悬液对改善小鼠哮喘效果较好,其作用机制可能与该药能够调节TLR4、My D88、p65蛋白表达,进而影响炎症和免疫反应进程有关。

桔梗皂苷D减轻大鼠肾缺血/再灌注损伤

目的探究桔梗皂苷D(PD)对大鼠肾缺血/再灌注损伤的保护作用。方法将大鼠分为假手术组、模型组,PD低、中和高剂量组(n=10)。模型组、低、中和高剂量组大鼠通过夹闭大鼠双侧肾蒂来建立缺血/再灌注损伤模型,假手术组大鼠进行相同的建模手术操作,但不夹闭肾蒂。建模前5 min对低、中和高剂量组大鼠分别腹腔注射12.5、25和50 mg/kg的PD。建模24 h后,检测大鼠的血清肌酐(Cr)和血尿素氮(BUN)水平,以及肾组织抗氧化标志物[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)]水平。苏木精-伊红(HE)染色评价肾组织病变。免疫组织化学染色检测肾组织caspase-3的表达,通过caspase-3阳性的细胞数量来评估肾小管上皮细胞的凋亡指数。RT-qPCR检测肾组织炎性因子白细胞介素-1β(IL-1β)、IL-6和IL-10的mRNA表达。Western blot检测Toll样受体4(TLR4)、髓样分化因子88(MyD88)、p65、p-p65、核因子κB(NF-κB)抑制因子(IκB)和p-IκB的表达。结果与假手术组相比,模型组大鼠的肾脏病变程度、血清Cr和BUN水平、肾小管上皮细胞的凋亡指数均升高(P<0.05)。与模型组大鼠相比,低、中和高剂量组大鼠的肾脏病变程度、血清Cr和BUN水平、肾小管上皮细胞的凋亡指数均降低(P<0.05)。与假手术组相比,模型组大鼠的肾组织中MDA水平、IL-1β和IL-6的mRNA水平和TLR4/MyD88/NF-κB信号通路蛋白表达水平均升高,SOD和GSH-Px水平以及IL-10的mRNA水平均降低(P<0.05)。与模型组大鼠相比,低、中和高剂量组大鼠的肾组织中MDA水平、IL-1β和IL-6的mRNA水平和TLR4/MyD88/NF-κB信号通路蛋白表达水平均降低,SOD和GSH-Px水平以及IL-10的mRNA水平均升高(P<0.05)。结论桔梗皂苷D对大鼠肾缺血/再灌注损伤有保护作用,其机制可能与提高抗氧化能力和抑制TLR4/MyD88/NF-κB信号通路有关。

Discovery of novel aporphine alkaloid derivative as potent TLR2 antagonist reversing macrophage polarization and neutrophil infiltration against acute inflammation

Toll-like receptor 2(TLR2)mediated macrophages regulate the protective immune response to infectious microorganisms,but the aberrant activation of macrophages often leads to pathological inflammation,including tissue damage.In this study,we identified antagonists of TLR2 by screening2100 natural products and subsequently identified Taspine,an aporphine alkaloid,as an excellent candidate.Furthermore,analysis of the 10 steps chemical synthesis route and structural optimization yielded the Taspine derivative SMU-Y6,which has higher activity,better solubility,and improved drug-feasible property.Mechanistic studies and seq-RNA analysis revealed that SMU-Y6 inhibited TLR2 over other TLRs,hindered the formation of TLR2/MyD88 complex,and blocked the downstream NF-κB and MAPK signaling pathway,thus suppressing the release of inflammatory cytokines.SMU-Y6 could stabilize TLR2 and bind to TLR2 protein with a Kdof 0.18μmol/L.Additionally,SMU-Y6 could efficiently reverse the M1 phenotype macrophage polarization,reduce the production of cytokines as well as infiltration of neutrophiles and alleviate the local inflammation in mice with acute paw edema and colitis.Collectively,we reported the first aporphine alkaloid derivative that selectively inhibits TLR2 with high binding affinity and superior drug-feasible property,thus providing an urgently-needed molecular probe and potential drug candidate for inflammatory and autoimmune disease therapy.

滋肾丸对肾盂肾炎大鼠Toll样受体及其下游信号转导通路的影响

目的:观察滋肾丸对肾盂肾炎大鼠肾脏和尿路组织Toll样受体4(TLR4)、Toll样受体5(TLR5)及其下游信号转导通路髓样分化蛋白MYD88,以及MYD88非依赖型途径激活NF-κB蛋白表达的影响,初步探讨其改善的分子机制。方法:建立肾盂肾炎大鼠模型,大鼠随机分为模型组、滋肾丸组、左氧氟沙星组,另设假手术组(n=10),假手术组及模型组灌胃纯净水,其他各组大鼠分别灌胃相应的药物,干预30 d,30 d后处死大鼠,双抗夹心法(ELISA)检测大鼠膀胱尿液分泌型免疫球蛋白A(SIg A)和尿道黏膜组织中IL-4、IL-6、IL-10的含量。采用免疫印迹(Western blot)法检测肾脏和尿路黏膜组织中TLR4、TLR5、MYD88、NF-κB蛋白表达。结果:(1)模型组大鼠尿SIg A水平明显高于假手术组(P<0.001)。滋肾丸组高于模型组(P<0.05)。左克组低于模型组高于假手术组,均无统计学差异。(2)模型组尿路黏膜组织中IL-4、IL-6、IL-10的含量均高于假手术组,与其相比差异有显著性统计学意义(P<0.001),两个治疗组与模型组相比,IL-4、IL-6、IL-10含量均下降,差异有统计学意义(P<0.05)。(3)在大鼠尿路黏膜和肾脏组织中,模型组TLR4、TLR4、My D88、NF-κB蛋白表达均高于假手术组,与其相比差异有统计学意义(P<0.05)。两个治疗组与模型组相比,TLR4、TLR4、My D88、NF-κB蛋白表达均下降,差异有统计学意义(P<0.05)。结论:通过上调TLR4、TLR5及My D88的表达,进而上调NF-κB的表达而引起炎性反应,可能为肾盂肾炎疾病进展的原因,滋肾丸可能下调TLR4、TLR5及My D88的表达,影响下游的炎性因子,促进刺激免疫系统分泌SIg A,对肾盂肾炎疾病起到保护作用。

维生素D对大鼠心血管保护作用及机制

目的了解维生素D对大鼠急性心肌梗死的保护作用机制。方法选取脂多糖(LPS)诱导A7R5细胞Toll样受体(TLR)4表达量最高的浓度和时间点,应用1×10-7mol/L的1,25(OH)2D3进行干预。建立大鼠心肌梗死模型,随机分为2组,I组:心肌梗死模型组(n=16)、II组:维生素D治疗组(n=16),另设III组:假手术组(n=15)。4w后处死大鼠,观察大鼠心肌梗死面积(MIS)及心肌血清酶学变化。real-time PCR和Western blot方法检测TLR4、髓样分化因子(MyD)88和核因子活化B细胞κ轻链增强子(NF-κB)的mRNA和蛋白表达。结果在LPS诱导基础上,维生素D处理0、12和24 h后,TLR4、MyD88和NF-κB的mRNA水平分别为(22.0±5.1)、(15.1±5.1)和(8.0±4.2);(28.8±5.7)、(20.1±4.4)和(14.0±3.7);(25.2±5.3)、(17.7±4.5)和(10.2±3.7);TLR4、MyD88和NF-κB的蛋白水平变化同mRNA水平一致;维生素D可使实验性心肌梗死大鼠的MIS从(37.89±3.24)降至(12.25±1.34)(P<0.01),并改善心肌血清酶学变化(P<0.01);维生素D能够下调实验性心肌梗死大鼠心肌组织TLR4、MyD88和NF-κB的mRNA表达,分别从(4.61±0.42)、(3.81±0.36)和(3.86±0.51)降至(2.73±0.25)、(2.17±0.41)和(1.63±0.39);TLR4、MyD88和NF-κB的蛋白水平变化同mRNA水平一致。结论维生素D通过下调TLR4表达及相关的Myd88和NF-κB途径对大鼠的心血管产生保护作用。