| Objective: Diabetic kidney disease(DKD)is one of the most common and serious complication of diabetes mellitus,yet the pathogenesis of DKD has not been elucidated.Inflammation is regarded as one of the important reasons for the onset of DKD in recent years.Chemerin is a chemotactic adipokine secreted mainly by adipose tissue,it can induce inflammatory cells to kidney via its own receptor.It has been suggested that the level of Chemerin may reflect the severity of renal inflammation to some extent.Tumor necrosis factor-ɑ(TNF-ɑ)is an important inflammatory cytokine in vivo,which can induce the production and releasing of other inflammatory cytokines,resulting in a vicious cycle of enlarged kidney inflammation,also accelerating the progress of DKD.The experiment was designed to examine the level of serum chemerin and TNF-ɑ in different stages of type 2 diabetic kidney disease patients and explore the pathogenesis of DKD.Methods:1 According to the T2 DM diagnosis and classification standard proposed by WHO in 1999,a total of 133 T2 DM patients were selected from the endocrinology department in the third hospital of hebei medical university from march to december in 2015.The T2 DM patients were further divided into three groups according to the urinary albumin/creatinine ratio(urinary A/Cr): simple type 2 diabetes mellitus(SDM)group(urinary A/Cr ratio was less than 2.5 mg/mmol for men,and urinary A/Cr ratio was less than 3.5 mg/mmol for women),microalbuminuria(mic-DKD)group(urinary A/Cr ratio ranged from 2.5 mg/mmol to 30 mg/mmol for men,and urinary A/Cr ratio ranged from 3.5 mg/mmol to 30 mg/mmol for women)and macroalbuminuria(mac-DKD)group(urinary A/Cr ratio was more than 30 mg/mmol for both men and women).SDM group consisted of 25 men and 22 women,with age 57.28±13.60 years,course 9.58±6.37 years;mic-DKD group consisted of 21 men and 20 women,with age 63.02±11.39 years,course 13.68±6.50 years;mac-DKD group consisted of 28 men and 17 women,with age 63.16±12.27 years,course 18.13±9.58 years.Patients with type 1 diabetes mellitus,infections,pregnancy,cancer,trauma,coronary heart disease,chronic liver disease,the use of angiotensin-converting enzyme inhibitors(ACEI)and angiotensin Ⅱ receptor blocker(ARB)and kidney diseases caused by other reasons were all excluded.45 healthy individuals in control group were collected from the medical center of the third hospital of hebei medical university during the same period,including 28 males and 17 females,with age 60.33±12.78 years.The constituent ratios of the age and gender between the normal control group and the T2 DM group were matched.2 The collection of nomal information and measurement of clinical indicators: gender,age,the duration of diabetes and past history.Overnight fasting for 10 h,the next morning all subjects were calculated systolic blood pressure(SBP),diastolic blood pressure(DBP),height,body weight,body mass index(BMI)= body weight / height squared.3 The blood biochemistry data: fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),serum creatinine(Scr),blood urea nitrogen(BUN)and uric acid(UA)were measured by automatic biochemical analyzer.4 The measurement of high sensitivity C-reactive protein(hs-CRP),HbA1 c and urinary A/Cr: hs-CRP was measuered by nephelometry.HbA1 c and urinary A/Cr were measuered by immunonephelometry.5 The measurement of Chemerin and TNF-ɑ: Serum level of Chemerin and TNF-ɑ were measuered by enzyme linked immunosorbent assay(ELISA).3ml venous blood were collected from all investigators after overnight 10 h,strenuous activity and stress were forbidden before blood sampling.Blood samples were keeping at room temperature for 1h,then centrifugal for 10 min at the speed of 3000r/min,serum was separated and finally stored at-20℃ refrigerator.Chemerin and TNF-ɑ were measured by enzyme-linked immunosorbent assay(ELISA): Chemerin kit was provided by Abcam(Shanghai)company(within batch coefficient of variation<10%,between batch coefficient of variation<12%).TNF-ɑ kit was supplied by Hangzhou Lianke biotechnology company(within batch coefficient of variation<3.8%,between batch coefficient of variation<5.0%).The test was performed in strict accordance with the instructions.6 Statistical analysis: All datas were analyzed by software SPSS17.0 version.The normality of data was tested at first,datas with normal distribution were expressed as mean±standard deviation(X ±s),non-normal data was expressed by the median(interquartile range);t-test was performed to compare measurement data between two groups;ANOVA was performed to compare normal data among groups;Rank sum test was performed for non-normal data;The relevance analysis of chemerin and TNF-ɑ concentration and other factors was estimated by the pearman or spearman correlation analysis;Logistic regession analysis was used to analyzed the risk factors of DKD,P<0.05 was defined as inclusion criteria,P>0.10 as the exclusion criteria.Results:1 There was no significant difference in constituent ratios of the age and gender between T2 DM group and NC group.Compared to these data in NC group,the level of course,BMI,DBP,FBG,HbA1 c,TC,TG,LDL-C,Scr,BUN,Urinay A/Cr and hs-CRP in the SDM group were significantly higher,but HDL-C was significantly lower;Compared with those data in SDM,the patients in mic-DKD group had higher level of course,BMI,SBP,WBC,FBG,HbA1 c,Urinay A/Cr,hs-CRP and lower HDL-C level;Compared with these datas in mic-DKD group,the level of course,FBG,SBP,HbA1 c,Urinary A/Cr,LDL-C,WBC and hs-CRP in the mac-DKD group were significantly higher,the level of HDL-C was lower.2 In NC group,Serum Chemerin concentration is 34.14±7.54 ng/ml,serum TNF-ɑ concentration is 103.99±20.43 pg/ml;Serum Chemerin concentration is 38.23±5.48 ng/ml,serum TNF-ɑ concentration is 134.42±27.31 pg/ml in SDM group;Serum Chemerin concentration is 42.69±8.05 ng/ml,serum TNF-ɑ concentration is 165.48±32.63 pg/ml in mic-DKD group;Serum Chemerin concentration is 47.32±9.11 ng/ml,serum TNF-ɑ concentration is 227.53±58.31 pg/ml in mac-DKD group.The level of Chemerin and TNF-ɑ increased gradually from NC group,SDM group,mic-DKD group to mac-DKD group,the difference between each two groups was statistically significant(all P<0.05).3 The serum Chemerin level is positively correlative with TNF-ɑ(r=0.420,P=0.000),hs-CRP(r=0.402,P=0.000),HbA1c(r=0.388,P=0.000),and duration(r=0.365,P=0.000),negatively correlative with HDL-C(r=-0.394,P=0.000).The serum TNF-ɑ level is positively correlative with urinary A/Cr(r=0.623,P=0.000),HbA1c(r=0.600,P=0.000),hs-CRP(r=0.569,P=0.000),Scr(r=0.537,P=0.000)and LDL-C(r=0.502,P=0.000),negatively correlative with HDL-C(r=-0.533,P=0.000).4 Logistic regression analysis showed that Chemerin(β=0.974,P=0.000),TNF-ɑ(β =1.812,P=0.000),WBC(β =1.524,P=0.000),Age(β =0.599,P=0.000),HbA1c(β=1.425,P=0.000),low HDL-C(β=-1.201,P=0.000)and hypertension(β=2.537,P=0.000)were independent risk factors of DKD.Conclusions:1 Chemerin and TNF-ɑ were involved in the pathogenesis of DKD.2 The level of Chemerin and TNF-ɑ may reflect a degree of severity for DKD. |
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