Irisin protects against neuronal injury induced by oxygen-glucose deprivation in part depends on the inhibition of ROS-NLRP3 inflammatory signaling pathway

Recent studies found that irisin, a newly discovered skeletal muscle-derived myokine during exercise, is also synthesized in various tissues of different species and protects against neuronal injury in cerebral ischemia. The NOD-like receptor pyrin 3 (NLRP3) inflammasome play an important role in detecting cellular damage and mediating inflammatory responses to aseptic tissue injury during ischemic stroke. However, it is unclear whether irisin is involved in the regulation of NLRP3 inflammasome activation during ischemic stroke. In the present study, PC12 neuronal cells were exposed to oxygen-glucose deprivation (OGD), exogenous irisin (12.5, 25, 50 nmol/L) or NLRP3 inhibitor glyburide (50, 100, 200 μmol/L) were used as an intervention reagent, NLRP3 was over-expressed or suppressed by transfection with a NLRP3 expressing vector or NLRP3-specifc siRNA, respectively. Our data showed that both irisin and its precursor protein fibronectin type III domain containing 5 (FNDC5) expression were significantly down-regulated (p < 0.05); but oxidative stress and ROS-NLRP3 inflammasome signaling were activated by OGD (p < 0.05); treatment with irisin or inhibition of NLRP3 reversed OGD-induced oxidative stress and inflammation (p < 0.05). However, these irisin-mediated effects were blunted by over-expression NLRP3 (p < 0.05). Taken together, our results firstly revealed that irisin mitigated OGD-induced neuronal injury in part via inhibiting ROS-NLRP3 inflammatory signaling pathway, suggesting a likely mechanism for irisin-induced therapeutic effect in ischemic stroke.     

妊娠期肝内胆汁淤积症孕妇血清和脐静脉血中鸢尾素水平及与临床指标的相关性

目的分析妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)孕妇血清及脐带血中鸢尾素水平及与临床指标的相关性。方法选取2017年11月至2019年11月深圳市龙华区人民医院收治的84例ICP患者为研究对象。依据ICP严重程度将患者分为轻症组(50例)和重症组(34例),另选择同时期来本院进行孕期保健的60例正常孕妇为健康组。采集全部孕妇空腹上臂静脉血样本及产后3 min内脐静脉血样本,分别进行血清鸢尾素水平及各临床指标的检测。比较各组间年龄、妊娠周期、体重指数(body mass index,BMI)、血压、胎儿体质量、新生儿Apgar评分、脐动脉阻力指数(resistance index,RI)、脐动脉收缩期最大血流速度/舒张期末期血流速度(S/D)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、总胆固醇(total cholesterol,TC)、脂蛋白、载脂蛋白A-I、载脂蛋白B、载脂蛋白比值、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)、γ-谷氨酰转移酶(gamma glutamyltransferase,GGT)、总胆汁酸、直接胆红素(direct bilirubin,DBil)、总胆红素(total bilirubin,TBil)、胆碱酯酶、肌酐、尿素、胱抑素C、葡萄糖及同型半胱氨酸(homocysteine,Hcy)水平。采用Pearson相关性分析上述临床相关指标与ICP孕妇血清及脐静脉中鸢尾素水平间的相关性。采用多因素Logistic回归分析ICP孕妇胎儿出生体质量低的影响因素。结果轻症组胎儿体质量、HDL-C和TG水平均显著低于健康组,ALT、AST、GGT及总胆汁酸水平均显著高于健康组(P均<0.05)。重症组妊娠周期、胎儿体质量、HDL-C及Hcy水平均显著低于健康组和轻症组,TG、LDL-C、TC、ALT、AST、ALP、GGT、总胆汁酸、DBil、TBil及肌酐水平均显著高于健康组和轻症组(P均<0.05)。3组患者脐静脉血中鸢尾素水平均显著低于血清中鸢尾素水平[健康组:(596.03±160.57)ng/L vs(902.47±153.17)ng/L;轻症组:(650.95±162.78)ng/L vs(1031.02±136.87)ng/L;重症组:(860.28±96.88)ng/L vs(1096.24±152.68)ng/L],健康组和轻症组患者脐静脉血中鸢尾素水平均显著低于重症组(P均<0.05)。ICP孕妇各项临床相关指标与血清中鸢尾素水平均无相关性(P均>0.05);胎儿体质量与脐静脉血中鸢尾素水平呈负相关(r=-0.386,P=0.042),脐动脉S/D值、TG、LDL-C、TC、ALT、AST、GGT、总胆汁酸及DBil与脐静脉血中鸢尾素水平呈正相关(P均<0.05)。Logistic回归分析表明血清中鸢尾素水平(OR=1.874,95%CI:1.361~8.242,P<0.001)及脐静脉血中鸢尾素水平(OR=1.868,95%CI:1.359~8.084,P<0.001)为ICP孕妇胎儿出生体质量低的独立危险因素,孕周为保护因素(OR=0.121,95%CI:0.032~0.951,P=0.113)。结论鸢尾素水平与ICP具有一定的关联。脐静脉血中鸢尾素水平均显著低于血清中鸢尾素水平,轻症ICP患者脐静脉血中鸢尾素水平均显著低于重症患者。ICP孕妇胎儿出生体质量降低可能与鸢尾素在能量及脂肪代谢方面的作用有关。     

Irisin对肥胖大鼠子宫内膜功能的影响

目的：观察鸢尾素（Irisin）对肥胖大鼠子宫内膜功能的影响。方法：选用成年雌性SD大鼠,采用高脂饲料建立肥胖模型;正常组给予正常饮食。将造模成功大鼠随机分为肥胖模型组（16只）和Irisin组（16只）,另设对照组（16只）。其中,Irisin组腹腔注射重组Irisin[100 ng/（g·d）×14 d],肥胖模型组和对照组腹腔注射生理盐水,并于注射前后记录大鼠体质量。后于动情期内合笼,于大鼠妊娠D5、D10天每组各处死8只大鼠,记录妊娠率及平均胚泡着床数,观察子宫内膜组织形态;检测大鼠子宫内膜白血病抑制因子（LIF）、整合素αvβ3蛋白及mRNA的表达。结果：Irisin组经腹腔注射Irisin 14 d后,大鼠体质量低于肥胖模型组,差异有统计学意义（P=0.035）。肥胖模型组平均胚泡着床数比对照组和Irisin组低,差异有统计学意义（均P＜0.05）。对照组大鼠子宫内膜宫腔饱满,胚胎发育好;肥胖模型组大鼠子宫腔间隙较大,胚胎发育不良;Irisin组大鼠子宫腔接近闭合,胚胎发育良好。肥胖模型组子宫内膜LIF、αvβ3的蛋白表达量和mRNA含量比对照组和Irisin组低,差异有统计学意义（均P＜0.05）。结论：Irisin可通过增加子宫内膜LIF、αvβ3的表达,从而改善肥胖大鼠子宫内膜容受性。     

血清乳脂肪球表皮生长因子8、鸢尾素对结直肠息肉病人复发的预测价值

目的 探究血清乳脂肪球表皮生长因子8(MFG-E8)、鸢尾素对结直肠息肉病人复发的预测价值。方法 以石家庄市中医院2021年6—12月收治的96例结直肠息肉病人为息肉组进行回顾性研究,另选取该院同期健康体检志愿者96例为对照组。采用酶联免疫吸附测定（ELISA）检测所有受试者血清MFG-E8、鸢尾素水平。术后随访半年,根据是否复发将息肉组病人分为复发组（32例）和未复发组（64例）,比较两组血清MFG-E8、鸢尾素水平。采用受试者操作特征曲线（ROC曲线）分析血清MFG-E8、鸢尾素对结直肠息肉病人复发的预测价值。结果 息肉组血清MFG-E8[(145.31±22.44)μg/L比（92.39±15.65）μg/L]水平明显高于对照组（P<0.05）,鸢尾素[（5.17±0.82）ng/L比（8.54±1.13）ng/L]水平明显低于对照组（P<0.05）。复发组血清MFG-E8[(163.39±26.31)μg/L比（136.27±17.51）μg/L]水平明显高于未复发组（P<0.05）,鸢尾素[（4.58±0.74）ng/L比（5.46±0.86）ng/L]水平...     

人血清Irisin和SFRP5水平变化与2型糖尿病合并肥胖患者的关系研究

目的 探讨人血清鸢尾素(Irisin)和分泌型卷曲相关蛋白5(secretory curl related protein 5,SFRP5)水平变化与2型糖尿病合并肥胖患者的关系。方法 选取2017年7月至2018年10月在孝感市中心医院内分泌科接受治疗的2型糖尿病合并肥胖患者38例作为观察组,再取同期健康体检者44例作为对照组。比较两组患者体重指数(body mass index,BMI)、空腹血糖(fasting plasma glucose,FBG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白-胆固醇(high density lipoprotein-cholesterol,HDL-C)、低密度脂蛋白-胆固醇(low density lipoprotein-cholesterol,LDL-C)水平,血清鸢尾素(Irisin)、分泌型卷曲相关蛋白5(secretory curl related protein 5,SFRP5)水平,并分析相关指标与血清Irisin、SFRP5水平的相关性。结果 观察组患者BMI、FPG、HbA1c水平均显著高于对照组(t值分别为28.71、16.74、13.87,P值均<0.05),HDL-C水平均显著低于对照组(t=4.640,P<0.05)。观察组患者血清Irisin、SFRP5水平显著低于对照组(t值分别为15.80、7.152,P值均<0.05)。观察组患者BMI、FPG、HbA1c与血清Irisin水平均呈显著负相关(r值分别为-0.803、-0.336、-0.644,P值均<0.05),HDL-C与血清Irisin水平均呈显著正相关(r=0.845,P<0.05);观察组患者BMI、FPG、HbA1c与血清SFRP5水平均呈显著负相关(r值分别为-0.745、-0.627、-0.614,P值均<0.05),HDL-C与血清SFRP5水平均呈显著正相关(r=0.711,P<0.05)。结论 血清Irisin、SFRP5的水平越低,2型糖尿病合并肥胖患者的病情越严重,故其对2型糖尿病合并肥胖患者的病情诊断有重要的临床意义。     

Irisin as a mediator between obesity and vascular inflammation in Chinese children and adolescents

Background and aimThis study aims to characterize the role of Irisin in obesity and early onset metabolic and vascular sequelae in Chinese children. Furthermore, we aim to examine whether Irisin mediate endothelial cells dysfunction and vascular inflammation which eventually leads to obesity.Methods and resultsWe quantified plasma Irisin levels using enzyme-linked immunosorbent assay (ELISA) among 85 lean and 120 obese children, and assessed the association of Irisin levels with anthropometric, metabolic, cardiovascular and inflammatory parameters of obese children comparing with lean children. We further characterized the markers for endothelial cells and inflammation between obese and lean children to assess potential correlations. In addition, a potential direct effect of Irisin on the expression of endothelial adhesion molecules was assessed in human coronary artery endothelial cells. Irisin levels from obese children was significantly lower than lean children, and this reduced Irisin levels is correlated with certain physical parameters of studied children. Moreover, we identified significant inverse associations between inflammation markers of endothelial activation with Irisin levels in obese children. Multiple regression analyses confirm Irisin serves as a strong predictor of SDS-SBP, Ang-2, ICAM-1, E-selectin and hsCRP levels, independent of SDS-BMI. Lifestyle intervention results in a significant improvement of these cardiovascular and inflammatory parameters, and these were accompanied by a significant improvement of Irisin levels and weight loss. Finally, in the mediation effect model, our data showed that Irisin changes act as partial mediators of the relationship between SDS-BMI changes and changes in inflammatory and endothelial parameters for ICAM-1, E-selectin and hsCRP after controlling for covariates. Likewise, on the cellular level, Irisin inhibition hsCPR, ICAM-1 and E-selectin expression in endothelial cells, whereas Ang-2, VCAM-1 and eNOS expression were unaffected.ConclusionsOur study showed that Irisin levels change may indicate the early stages of cardiovascular disease in obese children.     

鸢尾素对大鼠骨髓间充质干细胞 Sost基因表达及成骨分化的影响

目的探究鸢尾素（Irisin）对大鼠骨髓间充质干细胞（BMSC）Sost基因表达及成骨分化的影响。 方法设置Irisin不同浓度组（0、80、100、120 ng/mL）,细胞计数试剂盒（CCK-8）法选择Irisin的最佳实验浓度。用含有Irisin的培养液培养大鼠BMSC设置为实验组,对照组为单纯培养液培养,3、7、14 d进行茜素红、von Kossa钙盐染色;3、10 d采用反转录聚合酶链反应（RT-PCR）和Western bolt检测成骨相关基因mRNA及蛋白表达。分别采用单因素方差分析和t检验对数据进行统计分析。 结果（1）培养3 d时,100 ng/mL的Irisin促进大鼠BMSC增殖的效果明显（OD=0.951）,与对照组相比差异有统计学意义（F=102.52,P<0.05）;（2）实验组染色深度、钙结节大小和数量都明显高于对照组;（3）与对照组相比,实验组Sost mRNA及其蛋白表达水平明显下降,ALP、Lrp5、BMP2、Smad1的mRNA及其蛋白表达水平明显增高,差异均有统计学意义（P<0.001）。 结论（1）Irisin可抑制Sost基因的表达;（2）Irisin可在体外促进大鼠BMSC增殖和成骨分化;（3）Wnt和BMP信号通路可能在Irisin促进大鼠BMSC成骨分化中发挥作用。     

Evaluation of circulating irisin levels in healthy young individuals after a single 100,000 IU vitamin D dose

Irisin is a newly discovered hormone produced by the muscle. This hormone is involved in glucose metabolism, muscle strength and energy expenditure. As vitamin D is also known as a key player in that field, we aimed to see if a single dose of 100,000 IU of vitamin D would modify circulating levels of irisin in 29 young adults. Irisin was determined with the Phoenix Elisa assay at day 0, day 3, day 7 day 15 and day 28 after the loading dose. If we observed a significant increase in 25(OH)D levels (from 19.8 ± 8.4 ng/mL to 33.0 ± 8.5 ng/mL), irisin levels remained constant throughout the study (median 104.5 ng/mL, with values ranging from 69.9 to 390.9 ng/mL). Interestingly, one subject presented irisin values that were three times higher than all the others.     

The effect of fenugreek seed supplementation on serum irisin levels,blood pressure,and liver and kidney function in patients with type 2 diabetes mellitus: A parallel randomized clinical trial

ObjectivesThis study was designed to determine the effects of fenugreek seed (FS) on serum irisin levels, blood pressure, and liver and kidney function in patients with type 2 diabetes mellitus (T2DM).MethodsIn an 8-week randomized controlled clinical trial, T2DM patients (n = 50) were assigned to the intervention (5 g FS powder, 3 times a day) or control group. Both groups received anti-diabetic drugs and nutritional consults. Serum samples were collected and blood pressure was measured at baseline and end of the trial. Data on dietary intake and physical activity was determined using the questionnaires.ResultsCompared to the control group, FS consumption resulted in a significant decrease in fasting plasma glucose (FPG) (p = 0.024), as well as a significant change in serum alanine aminotransferase (ALT) (p = 0.02) and alkaline phosphatase (ALP) (p = 0.001). Within-group analysis showed a significant decrease in aspartate aminotransferase (AST) (p = 0.014), systolic blood pressure (SBP) (p = 0.001), and irisin (p = 0.001) in the FS group, and a significant increase in creatinine (Cr) (p = 0.001) and decrease in estimated glomerular filtration rate (eGFR) (p = 0.001) in the control group. FS consumption did not have any significant effect on diastolic blood pressure (DBP) and blood urea nitrogen (BUN).ConclusionFS intake has some beneficial effects on FPG, SBP, and some liver and kidney function tests in patients with T2DM. Further studies are required to investigate the effect of FS on irisin levels. Trial registration number http://www.irct.ir, code: IRCT20190618043924N1