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Study On The Expression Of Whole Blood MiR-155 In Patients With Type 2 Diabetes Mellitus, And Its Relationship With Vascular Complications

Posted on:2016-09-01Degree:MasterType:Thesis
Country:ChinaCandidate:L T GuoFull Text:PDF
GTID:2284330503451913Subject:Internal Medicine
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Background: Vascular complications are the main cause of disability and death in patients with type 2 diabetes mellitus(T2DM), the pathogenetic mechanism is complicated, recently "Inflammatory Hypothesis" has been widely recognized, all kinds of inflammatory factors on the role of diabetic complications has been further confirmed. Nuclear factor kappa B(NF-κB), Soluble Intercellular Adhesi on Molecule-1(s ICAM-1) are the important inflammatory factors. The latest research suggest that mi RNAs are the key factors in regulating cell function and the expression of proinflammatory and anti-inflammatory factors, participate in inflammation initiation and progression, and play a key role in inflammation regulatory. Mi RNAs is a length of about 22 nt of endogenous non-coding single-stranded RNA(nc RNA), it can target genes by combining to target gene-3’end untranslation section, degradation the target m RNA or repression target m RNA translation. Mi R-155 was a multifunctional inflammatory mi RNA, plays an important role in low-grade inflammatory disease.But the expression of mi R-155 in peripheral blood in T2 DM patients and the research about participation and regulation function in pathogenesis of T2 DM chronic vascular lesions were very few.Objective :Therefore, this research detected the m RNA expression of mi R-155,NF-κB, s ICAM-1 in peripheral blood with T2 DM patients and analysis there changes;discuss the possible mechanism of mi R-155 in the development of vascular complications, find new breakthrough point for the DM vascular complications and to provide new possibility treatment for clinical.Methods : 65 cases T2DM(The standards of diagnosis and classification according to the WHO of 1999 years) patients, male 35, female 30, aged 61.79 ± 10.55 years old, duration of DM 11.73 ± 7.93 years, Hb A1c(12.50 ± 8.09)%. Acrroding to Hb A1 c levels dividied into: Hb A1c<7%, 7%≤Hb A1c<9%, Hb A1c≥9%; Acrroding to duration of DM dividied into: duration of DM<10years, 10years≤duration of DM<20years, duration of DM≥20years. According to the vascular complications divided by: Simple T2 DM without vascular complications group(group A), Vascular complications group(group B); group B was futher divided into: microvascular lesion group(group B1), macrovascular lesions group(group B2), have microvascular and macrovascular complications at same time(group B3). Acrroding to the level of 24 h microalbuminuria in patients with vascular complications divided into: <30 mg / 24 h was urine albumin normal group, 30-300 mg / 24 h was microalbuminuria group, ≥300 mg / 24 h was macroalbuminuria group. All patients were no infection, tumor, no acute diabetic complications, no primary liver disease and non-diabetic kidney disease. Choose the age and body mass index(BMI) mached healthy person as control group, male 14, female 16, the blood glucose, blood lipid, blood pressure were normal in these subjects. The, blood pressure, height and weight of all research object were measured, and calculated BMI. All the subjects in the morning on an empty stomach after eight hours, take the elbow vein blood 5 ml, measured fasting blood glucose, Hb A1 c, hepatic and renal function, blood lipid, detected the m RNA expression level of whole blood mi R-155, NF-κB, s ICAM-1 with realtime RT-PCR; determined the 24 h urine microalbumin(24 h-m Alb) with transmission immune turbidimetric method.Results:1.The expression of mi R- 155,NF-κB, sICAM 1 in T2 DM group were significantly higher than those of control group(P < 0.05); Compared with Hb A1 c < 7% and duration of DM<10years group,the expression of mi R-155, NF-κB, s ICAM-1 were significantly higher in Hb A1 c ≥9 % group and duration of DM ≥2 0 years group(P < 0.05), and mi R- 155 in 7%≤Hb A1c<9% group is significantly higher than that of Hb A1 c < 7% group, s ICAM-1 in Hb A1c≥9% or 10 years≤duration of DM <20 years was also significantly higher than 7%≤Hb A1c<9% or duration of DM<10 groups.2.Compared to simple T2 DM without vascular complications group(group A),the level of mi R- 155, NF- κB, s ICAM-1 were significantly higher in T2 DM vascular lesions group(group B)(P < 0.05).The expression of mi R-155 in group B3 was higher than that of group A and group B2(P < 0.05), and mi R-155 in group B1 and B2 was also higher than that of group A, but there was no statistically significant difference(P>0.05); The expression of NF-κB in group B1,B2 and B3 were all significantly higher than that of group A, and also in group B3 was obviously higher than that of group B1 and B2(all P<0.05);the level of s ICAM-1 in group B1 and B3 was significantly higher than that of group A(P<0.05). The expression level of mi R-155, NF-κB, s ICAM-1 in microalbuminuria and macroalbuminuria group were higher than those of normal urine albumin group, and compared to microalbuminuria group, mi R-155 and s ICAM-1 was significantly higher than those of macroalbuminuria group(P < 0.05).3. The multiple correlation analysis showed that mi R-155 was significantly related to Hb A1 c, TG, NF- κB, s ICAM-1(all p<0.05); Multiple stepwise regression analysis showed that mi R- 155 was positively correlated with NF-κB, s ICAM-1(P< 0.05).Conclusions:The expression of mi R-155 in T2 DM patients increased, and with the extension of the duration of DM and Hb A1 c levels,mi R-155 increased gradually; the expression of mi R-155, NF-κB, s ICAM-1 in patients with vascular complications group were significantly higher than those without vascular complications group, in microvascular lesion + large vascular lesions group or macroalbuminuria group, the above three indicators increased more significantly too; multiple stepwise regression suggest that mi R-155 was obviously related to mi R-155, NF- κB, s ICAM-1,may participate in the development of diabetic vascular complications and mi R-155 closely related to NF-κB, s ICAM-1, so inflammation may be one of an important mechanism for the occurrence and development in diabetic chronic vascular lesions.
Keywords/Search Tags:Diabetetes mellitus, Vascular complications, MiR-155, Nuclear factor-κB, Soluble intercellular adhesion molecule-1
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