【作者】 李霞；

【导师】 张哲成；

【作者基本信息】 天津医科大学 ， 神经病学（专业学位）， 2017， 硕士

【摘要】 目的:我们通过对血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)与糖调节受损(IGR)周围神经病变的关系的研究,探讨炎性细胞因子TNF-α、IL-6在IGR周围神经病变的发病机制中的作用,并且结合TCSS评分进行相关分析,以期为IGR周围神经病变的早期诊断提供依据。方法:受试者均接受口服葡萄糖耐量试验(OGTT)检查,根据常规神经传导检测结果,选取70例IGR患者,其中IGR伴有周围神经病变(IGR-PN)组30例,男15例,女15例,平均年龄(59.8±10.4)岁;IGR不伴周围神经病变(IGR-NPN)组40例,男20例,女20例,平均年龄(57.7±9.2)岁;并选入40名健康者作对照,男20例,女20例,平均年龄(58.2±7.8)岁,各组间性别、年龄相匹配。分别测定3组受试者身高、体重,腰围,计算体重指数(BMI),记录血压,并于早晨空腹肘正中静脉取血检测空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C),糖化血红蛋白(HbAlc)和超敏C反应蛋白(hs-CRP)。利用西门子DPC1000仪器,使用西门子α肿瘤坏死因子测定试剂盒和白介素-6测定试剂盒,采用化学发光法分别对三组受试者进行血清TNF-α、IL-6检测。就三组患者的临床资料和生化指标检测结果进行比较分析,以糖调节受损是否合并周围神经病变为因变量,以FBG、OGTT-2h血糖、HbAlc、TG、TC、HDL-C、LDL-C、hs-CRP、IL-6及TNF-α为自变量,进行Logistic回归分析。通过多伦多临床评分系统(TCSS)对神经病变的诊断和严重程度分级进行评分,并将评分结果与血清TNF-α、IL-6水平做相关分析。同时对IGR-PN组与IGR-NPN组正中神经、尺神经、胫后神经以及腓肠神经的感觉及运动神经传导速度和波幅检测结果进行比较分析,并与血清TNF-α、IL-6水平做相关分析。对腓肠神经病SNCV与TCSS评分做相关分析。结果:1.IGR组血清TNF-α、IL-6水平均高于健康对照组;IGR-PN组血清TNF-α和IL-6水平高于IGR-NPN组均(P<0.05),差异有统计学意义。2.以IGR是否合并周围神经病变因素为因变量,以FBG、OGTT2h血糖、HbAlc、TG、TC、HDL-C、LDL-C、hsCRP、IL-6和TNF-α为自变量,进行多因素Logistic回归分析显示,影响IGR是否合并周围神经病变的因素为TNF-α(OR=0.893,p=0.009),IL-6(OR=0.876,p=0.041),TNF-α和IL-6对IGR合并周围神经病变分别独立起作用。3.IGR-PN组、IGR-NPN组TCSS评分均明显高于对照组(P<0.01),IGR-PN组TCSS评分显著高于IGR-NPN组(P<0.05),差异均有统计学意义。4.电生理检查显示神经传导速度在IGR-PN组与IGR-NPN组相比较,腓总神经运动神经传导速度(MNCV)及胫后神经感觉神经传导速度(SNCV)均显著降低(P<0.05)其他神经速度差异无显著性意义;在IGR-PN组与IGR-NPN组比较结果显示,腓总神经CMAP波幅和正中神经和胫后神经SNAP波幅均显著降低(P<0.05),而其他神经CMAP波幅差异无显著性意义。腓肠神经病SNCV与TCSS评分呈显著性负相关。5.血清TNF-α、IL-6水平均与糖调节受损患者TCSS评分呈显著正相关,6.血清TNF-α水平与腓肠神经SNCV和胫后神经SNAP波幅呈显著性负相关。血清IL-6水平与腓肠神经SNCV呈显著性负相关。结论:1.TNF-α、IL-6可能具有促进糖调节受损患者伴发周围神经病变的作用,2.TNF-α、IL-6可能是糖调节受损性周围神经病的独立危险因素。3.TNF-α、IL-6与糖调节受损周围神经病变神经纤维损伤程度相关4.TNF-α、IL-6可能是糖调节受损性周围神经病的可靠的生物学标志物。更多还原

【Abstract】 Objective: In this study,we measured serum level of tumor necrosis factor alpha(TNF-α)and interleukin 6(IL-6)in normal control and IGR patients with or without peripheral neuropathy to explore the mechanism of TNF-α and IL-6 in the process of peripheral neuropathy.Correlation analysis of TNF-α and IL-6 with TCSS score in order to provide evidence for early diagnosis of IGR peripheral neuropathy.Methods: All of subjects were conformed with normal oral glucose tolerance test(OGTT)results.A total of 70 IGR patients received the conventional nerve conduction test,including 30 patients with peripheral neuropathy(PN),40 patients without peripheral neuropathy(NPN);The other 40 healthy were recruited as controls.The demographic data including height,weight,waist circumference,body mass index(BMI)and blood pressure was recorded in the 3 groups were recorded.Their Fasting blood glucose(FBG),glycosylated hemoglobin(Hb Alc),triglycerides(TG),total cholesterol(TC),high density lipoprotein(HDL-C),low density lipoprotein cholesterol(LDL-C)and high-sensitivity C-reactive protein(hs-CRP)were measured.Their serum TNF-α and IL-6 levels were measured by chemiluminescence method.The motor conduction of median nerve,ulnar nerve,common peroneal nerve,and the sensory conduction of median nerve,ulnar nerve,posterior tibial nerve,and sural nerve of all subjects were measured by the Dantec Keypoint Workstation.the severity of neuropathy were graded according to Toronto clinical scoring system(TCSS).Result:1.The serum TNF-α and IL-6 in IGR patients were higher than control group;And serum TNF-α and IL-6 levels in IGR-PN group were higher than IGR-NPN group(p<0.05).2.Multi factors logistic regression analysis showed that TNF-α(OR=0.893,p =0.009),IL-6(OR=0.876,p =0.041)were independent factors effecting whether IGR could combine with peripheral neuropathy.the neuropathy score in IGR-PN group was significantly higher IGR-NPN group with significant difference(p<0.01).3.The scores of TCSS in IGR-PN group and IGR-NPN group were significantly higher than those in control group(p <0.01),and the score of TCSS in IGR-PN group was significantly higher than that in IGR-NPN group(p <0.05),the difference was statistically significant.4.Neuropathy Comparison.Nerve conduction velocities in IGR-PN group were compared with IGR-NPN group.Motor nerve conduction velocities(MNCV)in common peroneal nerve and sensory nerve conduction velocities(SNCV)in posterior tibial nerve were significantly decreased(p < 0.05).Amplitudes in IGR-PN group were compared with IGR-NPN group.CMAP amplitude in common peroneal nerve and SNAP amplitude in median nerve and posterior tibial nerve were significantly decreased(p < 0.05).There was a significant negative correlation between SNCV and TCSS scores in sural neuropathy.5.Further Pearson correlation analysis showed TNF-α levels significantly positive related with TCSS score(r=0.331).6.Correlation of biomarker TNF-α with nerve conduction studies in IGR-PN group showed significant negative correlation with sural SNCV and posterior tibial nerve SNAP amplitude.Correlation of biomarker IL-6 with nerve conduction studies in IGR-PN group showed significant negative correlation with sural SNCV.Conclusion:1.TNF-α and IL-6 could aggregate peripheral neuropathy in impaired glucose regulation patients;2.TNF-α and IL-6 might be independent risk factors for peripheral neuropathy in glucose regulation impaired patients;3.TNF-α and IL-6 are associated with the degree of nerve damage induced by glucose regulated impaired;4.TNF-α,IL-6 may be a reliable biomarker for peripheral neuropathy in glucose regulation impaired patients.更多还原