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Objective:To observe the effect of percutaneous auricular vagus nerve stimulation on myocardial structural remodeling, electrical remodeling and apoptosis in rats of heart failure with preserved ejection fraction, and to explore the relationship between this effect and oxidative stress.Methods:The arteriovenous fistula was closed by ligation two weeks after establishment in SD rat.By increasing cardiac volume load in the short term, a rat model of heart failure with preserved ejection fraction was constructed.Forty rats were randomly divided into four groups, with 10 rats in each group: sham operation group(S), abdominal aorta-inferior vena cava fistula + closure group(AVF+ L), abdominal aorta-inferior vena cava fistula + closure+ percutaneous auricular vagus nerve stimulation group(AVF+ L+ tVNS)and abdominal aorta-inferior vena cava fistula + closure+ percutaneous auricular vagus nerve stimulation + acetylcholine M 2 receptor antagonist group(AVF+ L+ tVNS+ M -). Rats in the AVF+ L+ tVNS group received percutaneous vagal nerve stimulation on the basis of those in the AVF+ L group.Rats in the AVF+ L+ tVNS+ M - group received daily injection of acetylcholine M 2 receptor antagonist mesotramine(0.5mg/Kg)into tail vein on the basis of those in the AVF+ L+ tVNS group.The parameters of cardiac structural remodeling and electrical remodeling in each group were obtained by cardiac ultrasound and cardiac electrophysiological stimulator.Enzyme-linked immunosorbent assay(ELISA)was used to detect the values of B-type natriuretic peptide precursor(NT-proBNP)and oxidative stress-related indicators in each group.hematoxylin-eosin(HE)staining was used to observe the damage of myocardial structure, disorder of cell arrangement and infiltration of inflammatory cells.Cardiomyocyte apoptosis was observed by TdT-mediated dUTP nick end labeling(TUNEL)staining and apoptosis index was calculated.reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting were used to detect the mRNA and protein expression of B cell lymphoma / leukemia-2(BCL-2)and apoptosis promoting gene(BAX)in BCL-2 gene family. Results:The rats in the AVF + L group developed heart failure characterized by ventricular wall hypertrophy and diastolic dysfunction, and the left ventricular ejection fraction(LVEF)was >50 %.The rat heart failure model with preserved ejection fraction was successfully established.HE staining showed that the myocardial tissue structure damage, cell arrangement disorder and inflammatory cell infiltration were obvious in AVF+ L group, while the pathological changes of myocardial tissue in AVF+ L+ tVNs were significantly less than those in AVF+ L group.Compared with AVF+ L group, in the AVF+ L+ tVNs, the value of NT-proBNP decreased[(301.25 ± 16.07)ng/L vs.(79.33±5.63)ng/L, P<0.05], the value of E/A increased(1.28 ± 0.06 vs.1.66 ±0.05, P<0.05), the expression of BCL-2 mRNA[0.08(0.07, 0.08) vs.0.70(0.64, 0.76), P<0.05]and BCL-2 protein(0.19±0.03 vs.0.46±0.04, P<0.05)both increased, the expression of BAX mRNA(5.00±0.32 vs.2.14±0.36, P<0.05)and BAX protein(0.76±0.04 vs.0.43±0.05, P<0.05)both decreased, while the apoptotic index was also decreased(16.26±0.32 vs.7.04±0.24, P<0.05). Compared with AVF + L group, the indexes of myocardial structural remodeling, electrical remodeling and oxidative stress were decreased in AVF + L + tVNs group(P<0.05). Compared with AVF + L group, there was no significant difference in the above indexes in AVF + L + tVNS + M - group( P>0.05). Conclusions:tVNS can alleviate myocardial structural remodeling, electrical remodeling and apoptosis in HFpEF rats, which may be related to the reduction of oxidative stress response activity.
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Objective To investigate the neuroprotective effect and mechanism of liraglutide on diabetic rats. Methods 24 healthy male SPF Goto-Kakizaki (GK) rats with random blood glucose greater than 11.1 mmol/L were selected as the experimental group, and randomly divided into diabetes mellitus group ( n＝12) and liraglutide group (n＝12). Ten healthy male SPF Wistar rats with the same age and weight as GK rats were selected as normal control group. After adaptively feeded for 2 weeks, the liraglutide group was given liraglutide (400 μg·kg－1·d－1, subcutaneous injection), while the control group and diabetes mellitus group were given the same volume of saline, and continued to be administered for 8 weeks. After 10 weeks, data and biochemical indicators were recorded. Effects of liraglutide on learning and memory in diabetes mellitus rats were detected by Morris water maze test. HE staining observed the hippocampal neurons morphology. Western blotting method detected the expression of p- IκB kinase (IKK) β, p-NF-κB, NF-κB, Klotho, and PRX2 in hippocampus. Results Morris water maze test showed that liraglutide can improve the spatial learning and memory ability of diabetes mellitus rats. HE staining showed that liraglutide significantly reduced the pathological damage of hippocampal neurons of diabetes mellitus rats. Western blotting showed that liraglutide inhibited NF-κB signaling pathway in hippocampus of diabetes mellitus rats. The expression of Klotho protein in hippocampus of diabetes mellitus group was significantly lower than that of control group, while the expression of PRX2 protein was higher than control group (t＝8.298,－7.398,all P<0.01). The expression of Klotho and PRX2 protein in hippocampus of liraglutide group were higher than diabetes mellitus group (t＝－13.059, 14.113, all P<0.01). The expression of Klotho protein of liraglutide group was similar to that of control group ( t ＝ －1. 137, P>0. 05 ). The expression of PRX2 protein was significantly higher than control group (t＝－28.055, P<0.01). Conclusions Liraglutide may enhance the expression of antioxidant stress protein including Klotho and PRX2, by inhibiting NF-κB signaling pathway in hippocampus of diabetes mellitus rats, reduced oxidative stress and improved the injury of hippocampal neuronal in diabetes mellitus rats, which seems to play a neuroprotective effect, to prevent and delay the occurrence of diabetic encephalopathy.
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Objective To investigate the association of serum ghrelin level with cognition, hippocampal volume, and proton magnetic resonance spectrum ( [ 1 H ]-MRS ) in patients with type 2 diabetes mellitus ( T2DM) . Methods The T2DM patients cared at the Wuhan Fourth Hospital were recruited. Data on demographic characteristics and clinical parameters were collected. Ghrelin was measured by ELISA assay. Cognitive performance was assessed by the Montreal Cognitive Assessment ( MoCA ) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The changes of metabolites in hippocampus were detected by [1 H]-MRS, including N-acetyl asparate ( NAA) , choline ( Cho) , myo-inositol ( MI) , creatine ( Cr) . All patients were divided into 2 groups[cognitive impairment (CI) and non-cognitive impairment (NCI) groups] by MoCA. Results (1) Compared with patients in NCI group, the serum ghrelin level, bilateral hippocampal volume, and NAA/Cr ratio of [1H]-MRS metabolites in CI group were decreased, but MI/Cr and Cho/Cr ratios were increased(all P<0.05). (2) Serum ghrelin was positively correlated with a variety of RBANS scores ( including immediate memory, attention, delayed memory, and total scores) , bilateral hippocampal volume, and NAA/Cr ratio of [ 1 H]-MRS metabolites in T2DM patients, but it was negatively correlated with MI/Cr ratio and Cho/Cr ratio ( all P<0. 05 ) . ( 3 ) Logistic regression analysis showed that ghrelin was a protective factor of cognition in T2DM patients. Conclusions T2DM patients with cognitive impairment had lower levels of ghrelin, and serum ghrelin was postively correlated with their cognitive performance, hippocampal volume, and [1 H]-MRS metabolites, suggesting that serum ghrelin may be involved in the occurrence and development of cognitive dysfunction in patients with T2DM.
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AIM: To investigate whether rs7903146 polymorphisms in transcription factor 7-like 2 (TCF7L2) gene are associated with susceptibility to type 2 diabetes mellitus (T2DM) in Chinese Uygur population.METHODS: In this case-control study, 935 cases of T2DM patients were recruited in T2DM group, and 971 healthy examination individuals were selected as normal control.The TCF7L2 gene polymorphism was detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrum.RESULTS: Significant differences in the frequencies of CC, CT and TT genotypes and the frequencies of C and T alleles on TCF7L2 rs7903146 were found between T2DM group and control group(P<0.05).As compared with C allele, the patients with T allele had a significantly higher risk of T2DM with OR of 1.190 (95% CI: 1.034~1.371).As compared with CC genotype, the patients with CT genotype had a significantly higher risk of T2DM with OR of 1.374 (95% CI: 1.122~1.683), and the patients with CT+TT genotype had a significantly higher risk of T2DM with OR of 1.307 (95% CI: 1.090~1.567).The levels of fasting plasma glucose, serum creatinine and blood urea nitrogen were higher in all participants with CT+TT genotype of rs7903146 than those with CC genotype, which showed a significant difference (P<0.05).CONCLUSION: The polymorphisms of rs7903146 in TCF7L2 gene may be associated with T2DM in Uygur population from Xinjiang region.The T allele and CT genotype of rs7903146 are the risk factors for T2DM.
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Objective To investigate the correlation between TCF7L2 gene rs3814570 polymorphisms with type 2 diabetes mellitus(T2DM) in Uygur population of Xinjiang area.Methods By adopting the case-control study design,949 cases of T2DM were recruited as the observation group and 963 individuals Undergoing healthy physical examination were selected as the control group.The TCF7L2 gene polymorphism was detected by matrix-assisted laser desorption/ionization-time of flight(MALDI-TOF).Results The statistical differences in frequencies of CC,CT and TT genotypes and the C and T allele frequencies on TCF7L2 rs3814570 were found between the T2DM group and control group(P＜0.05).The risk of suffering from T2DM in the carriers of CT genotype was 0.331 times of that in the carriers of CC genotype(OR =0.331,95 ％ CI:0.166-0.661,P =0.002),the risk of suffering from T2DM in the carriers of TT genotype was 0.539 times of that in the carriers of CC genotype(OR=0.539,95％CI:0.348-0.834,P=0.005),and the risk of suffering from T2DM in the carriers of T allele was 0.501 times of that in the carriers of C allele(OR=0.501,95 ％ CI:0.377-0.664,P＜ 0.01).Among all subjects,the FPG level of the CT + TT genotype group on TCF7L2 gene rs3814570 locus was significantly lower than that of the CC genotype group(P＜0.05).Conclusion The rs3814570 locus in TCF7L2 gene may be associated with T2DM occurrence in Uygur population of Xinjiang area,the T allele and TT genotype might be protective factors of T2DM.
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Objective To investigate the association of serum dehydroepiandrosterone sulfate( DHEA-S) with the cognition in male type 2 diabetes mellitus(T2DM)patients. Methods 99 male patients cared at Tangshan Gongren Hospital and another 97 male healthy controls without T2DM from the medical examination center were recruited. Data on demographic characteristics and clinical parameters were collected, DHEA-S was measured by radioimmunologic assay. Cognitive performance was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS). Results (1) Serum DHEA-S levels were lower in male T2DM patients than that of controls[(2. 66 ± 0. 78 vs 4. 02 ± 1. 24) μmol/ L, P<0. 01];(2) Compared with controls, RBANS scores including immediate memory(79. 24 ± 17. 47 vs 86. 25 ± 15. 21, P<0. 01), visuospatial/ constructional(83. 98 ± 17. 98 vs 97. 24 ± 11. 51, P<0. 01), attention(96. 04 ± 14. 65 vs 101. 45 ± 13. 93, P<0. 01), delayed memory (89. 28 ± 11. 74 vs 97. 41 ± 9. 41, P<0. 01), and total scores(85. 85 ± 11. 46 vs 94. 60 ± 10. 91, P<0. 01)were all lower in male T2DM patients;(3) RBANS scores including delayed memory(84. 53 ± 12. 23 vs 93. 94 ± 9. 18, P<0. 01)and total scores(80. 33 ± 10. 91 vs 91. 26 ± 9. 25, P<0. 01)in T2DM patients with low-level DHEA-S(DHEA-S-L)were all lower than those of patients with high-level DHEA-S;(4)Male T2DM patients with cognitive impairment had lower levels of DHEA-S than patients without cognitive impairment(2. 31 ±0. 79 对 2. 90 ±0. 67, P<0. 01);(5) In male T2DM patients, DHEA-S was positively correlated with delayed memory(r = 0. 252, P = 0. 019) and total scores(r=0. 258, P= 0. 016). Conclusion Male T2DM patients are with lower serum DHEA-S levels and worse cognitive performance, and serum DHEA-S was positively correlated with their cognitive performance, suggesting that serum DHEA-S may be involved in the cognitive deficits of male T2DM patients.
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Objective To investigate the changes of C- reactive protein( CRP ) and homocysteine ( Hcy)in the type 2 diabetes with depression,and its clinical significance and potential mechanism. Methods One hundred and twenty-four cases with type 2 diabetes were divided into the depression group(63 cases)and non-depression group( 61 cases ) according to the Self-Rating Depression Scale and verified by Self-Rating Anxiety Scale. The information including age,sex,education degree,body mass index,course of disease and the number of complications were recorded. The levels of CRP,Hcy,fasting plasma glucose( FPG ),glycosylated hemoglobin(HbA1c)and blood lipid were measured. The depression group was divided into mild,medium and heavy group to compared the changes of Hcy and CRP. Results The levels of Hcy,HbA1c and the number of complications in depression group were 11. 5( 8. 6,15. 6 )μmol/L,( 10. 13 ± 2. 17 )%,and 2( 1,3 ) respectively,higher than that of non-depression group(8. 6(7. 4,11. 2)μmol/L,(9. 33 ± 2. 20)%,1(0,2)), while the education degree of depression group((9. 75 ± 3. 36)years)was lower than that of non-depression group((11. 56 ± 3. 73)years),and the differences were significant( t/Z = -3. 537,0. 952,-2. 339,0. 228 respectively;P ﹤0. 05). The levels of Hcy in mild,medium and heavy depression group were(8. 75(7. 45, 10. 45)μmol/L,12. 2(8. 90,14. 40)μmol/L,19. 50(14. 33,28. 03)μmol/L respectively and the difference was significant(F =25. 963,P =0. 000). No significance difference was found in terms of CRP level(2. 35 (1. 10,4. 92)mg/L,3. 25(1. 11,5. 68)mg/L,2. 32(1. 27,5. 41)mg/L;F=0. 194,P=0. 907). There was significant correlation between depression scores and Hcy( r=0. 615,P=0. 000). Conclusion Type 2 diabetes with depression is associated with the level of blood glucose,education degree and the course of disease. Hcy,not CRP is an independent risk factor of type 2 diabetes with depression.