| Objective:High blood sugar generates advanced glycation end products(advanced glycation products, AGEs) by non-enzymatic glycosylation pathway can lead to diabetic peripheral neuropathy. However,once combined with tissue, AGEs can cause irreversible damage to nerve tissue, and the current generation of drugs to suppress the effect of AGEs was not so ideal. Therefore, to reduce AGEs precursor-MGO, may be a new target to prevent the development of diabetic peripheral neuropathy. The elevated levels of MGO can quickly generate AGEs and cytotoxicity which irreversibly modified proteins and antivated NF-k B signaling pathway, resulting in releasing a series of inflammatory cytokines such as inflammatory TNF-α and the like. In recent years, a large number of studies have shown that inflammatory can induce neuropathic pain, and it may suggests that MGO-NF-k B-inflammatory signaling pathways may be involved in the pathogenesis of diabetic neuropathic pain. So, to observe the serum level of methylglyoxalã€nuclear transcription factor-k B and the activity of typical inflammatory cytokines tumor necrosis factor-αlpha on mononuclear cells in patients with painful diabetic neuropathy, simultaneously analyse whether there is some correlation between the positive indicators,, and to further explore the mechanism of MGO-NF-k B-inflammatory signaling pathway in patients with diabetic neuropathy groups, especially painful diabetic neuropathy group in this study. Methods:The study screens 114 in-ward patients with T2 DM and diabetic peripheral neuropathy who are hospitalized in department of endocrinology of the second artillery force general hospital from February 2014 to December 2014. They are divided into three groups based on the different diagnosis criteria in total:(1) T2 DM group: 33 cases, include 21 males and 12 females;(2) DPN group: 51 cases, 24 males, 27 females;(3) PDN group: 30 cases, 20 males, 10 females.(4) The normal control group(NC group) : 30 cases, 12 males, 18 females; the healthy population of physical examination are from the same period in our hospital, who have no any diaease. Each group select on the basic balance either gender or age, which is consistent with the principles of the matches in the statistical significance. Research indicators:(1) The same physician collect height, weight, blood pressure values;(2) biochemical indicators: collect the blood to send to the laboratory and make use of the appropriate instrument to detect liver function, kidney function, lipids, blood glucose and other variables in the fasting state,(3) glycated hemoglobin(Hb A1c): make use of the high performance liquid method to test;(4) main observing indicators: collect 5ml fasting blood by the EDTA anticoagulated tube. The levels of MGO, NF-k B, TNF-α were measured by ELISA France and RT-PCR assays. Simultaneously, take up Pearson to analyse their correlations. Establish a database to application processing variables in SPSS software, whether P value was statistically significant, its judgement was based on the results. Results:First, the general clinical data1. T2 DM group, DPN group, PDN group compared with NC group, the levels of BMI, SBP, DBP, TG, FPG and Hb A1 c were significantly higher, by the statistics treatment, P <0.05, which exist the significant difference and suggest that the metabolic disorders were associated with the incidence of T2 DM. About on the levels of TC, LDL, Age, by the statistical treatment, P>0.05, they have no statistic significance among T2 DM group, DPN group and PDN group.2. the duration of DPN group, PDN was significantly longer than that of T2 DM group, by the statistical treatment, P<0.05, there was significant difference and it suggests that the course are the risk factors of the occurrence of diabetic neuropathy. The levels of age, sex, body mass index, blood pressure, blood lipids and blood glucose, by the statistical treatment, P>0.05, they have no statistic significance among the three groups, so as to ensure comparability.Secondly, the serum changes of MGO1. there was difference in NC group, T2 DM group, DPN group, PDN groups compared between groups, by the statistical treatment, P<0.01, the level of MGO was statistically significant among four groups.2.Compared DPN group(62.7±9.7pg/ml) and T2DM(44.0±4.6pg/ml) group: the MGO was significantly increased, by the statistical treatment, P<0.01, suggesting that MGO may play a role in the pathogenesis of DPN.3. PDN group(102.4 ± 7.7pg/ml) compared with DPN group(62.7±9.7pg/ml) : the serum levels of MGO was significantly increased, by the statistical treatment, P<0.01, showing that MGO may be also involved in PDN.Three, TNF-α gene expression and the serum changes of NF-k B1. The activity of TNF-α and the serum levels of NF-k B existed the difference in the NC group, T2 DM group, DPN group, PDN group between the groups by the statistical treatment, P<0.01.2. DPN group(5.9±0.7 folds)(487.2±146.0pg/ml) and T2DM(3.8±0.4 folds)(388.7±133.8pg/ml) group: The activity of TNF-α and the serum level of NF-k B were significantly elevated by the statistical analysis, P<0.01, showing that inflammation may have an effect on the pathogenesis of DPN.3. The activity of TNF-α and the serum level of NF-k B in PDN group(7.9±0.8folds)(807.3±163.3pg/ml) were significantly higher than DPN group(5.9±0.7folds)(487.2±146.0pg/ml), by the statistics treatment, P<0.01, and the difference were statistically significant, suggesting that inflammation may be induced in the occurrence of PDN.Fourth, the correlation analysis1. The correlation analysis of MGO: they have correlations among MGO and TG, fasting glucose, Hb A1 c, BMI, SBP, the course and HDL. The values of r were 0.544, 0.264,0.481,0.155,0.248,0.437,-0.329, by the statistical treatment, P<0.05; age, DBP, TC, which are not related to MGO,by the statistical treatment, P>0.05.2. The correlation analysis of TNF-α: TNF-α and TG, fasting glucose, Hb A1 c, BMI, SBP, the course was positively correlated, and the values of r were 0.553,0.289,0.518,0.141,0.216,0.488, by the statistical treatment, P<0.05; and there is a negative correlation between high-density lipoprotein(HDL) and TNF-α, Statistically, r=-0.344, P<0.01; It’s not associated with age, LDL, DBP, TC, etc( P>0.05).3. The correlation analysis of NF-k B: they have positive correlations and negative correlation between NF-k B and TG, fasting glucose, Hb A1 c, SBP, the course and HDL, the values of r were 0.514,0.193,0.405,0.246,0.364,-0.314, by the statistical treatment, p values was less than 0.05; Age, LDL, DBP, TC were not related to NF-k B,by the statistical treatment, P>0.05.4. MGO and NF-κB(r=0.913, P=0.001), TNF-α(r=0.924, P=0.001) were in accord with the linear trend. The levels of NF-k B and TNF-α had a linear relationship which showed that they were positively correlated(r=0.917, P<0.01); unanimously the three trends of MGO, NF-k B and TNF-α, were mutually positive. Control after the relevant factors TG, fasting glucose, Hb A1 c, BMI, SBP and course, TNF-α is still independently associated with MGO, and by the statistical treatment, r=0.859, P<0.01. Conclusions:1. The serum level of MGO was significantly increased in the PDN group, showing that MGO may be involved in the pathogenesis of painful diabetic neuropathy and to reduce the formation of MGO can prevent the currence of diabetic neuropathic pain.2. The activity of TNF-α and the levels of NF-κB were significantly higher in the PDN group, suggesting that inflammation has an effect on PDN.3. MGO, NF-κB, TNF-α in PDN group was significantly higher than that of in T2 DM group, indicating they may play an important role in PDN.4. Not only MGO and NF-κB, TNF-α activity was positively correlated, but also NF-κB was positively correlated with TNF-α activity. The changes of three indicators were the same trend, suggesting that MGO might induce neuropathic pain by the mechanism of inflammatory. |
