过表达肌浆网钙ATP酶治疗实验性慢性缺血性心力衰竭

Objective Chronic myocardial ischemia (CMI) has become the most importat cause of heart failure (HF) all over the world. The aim of the current study was to investigate the effects of Sarcoendoplasmic reticulum calcium ATPaee 2a (SERCA2a) gene transfer on cardiac function and endoplasmic reticulum stress (ERS) associated myocardial apoptosis in a minipig HF animal model induced by CMI. Methods HF was induced in minipigs by implantation of ameroid constrictor in the initial segment of left anterior descending (LAD) branch of coronary artery. After confirmation of myocardial perfusion defects and cardiac function impairment by myocardial perfusion imaging and echocardiography, animals were divided into 4 groups (n =4 each): HF group, HF + enhanced green fluorescent protein (EGFP) group,HF + SERCA2a group, and shamed animals as control group. A total amount of 1×1012 v.g. Of rAAV1EGFP or rAAV1-SERCA2a were injected intramyocardially to each animal of HF + EGFP and HF +SERCA2a groups. Sixty days after gene transfer, protein level and activity of SERCA2a were examined,cardiac functions and changes of serum inflammatory and neuro-hormonal factors were determined. Apoptotic index of the ischemic myocardium, protein levels of ER stress marker glucose regulated protein 78 ( GRP 78) and ER stress specific apoptotic marker caspase-12 were also assayed. Results At the study end,echocardiographic and hemodynamic measurements indicated a significant improvement of both cardiac systolic and diastolic function in HF + SERCA2a group compared with HF/HF + EGFP groups [LVEF (60.2±8.6)%vs (44.2±7.1)% and (46.8±6.7)%, Ev/Ay 1.28±0.24 vs 0.77 ±0.17 and 0.80±0.21, +dp/dtmax(2713.9 ±434.0) mm Hg/s ( 1 mm Hg =0.133 kPa) vs (1892.3 ±434.2) mm Hg/s and (1931.2±397.4)mm Hg/s, -dp/dtmax (1422.1±334.4) mm Hg/s vs (848.3±308.3) mm Hg/s and (849.5±278.3)mm Hg/s, P＜0.05], along with increase in both SERCA2a protein level (1.13±0.26 vs 0.73 ±0.17 and 0.64±0.18, P＜0.05) and activity [(16.2±5.5) IU/ml vs (7.9±3.1) IU/ml and (7.5 ±2.8)IU/ml, P ＜0.05] compared with HF/HF + EGFP groups. Serum concentrations of inflammatory factor tumor necrotic factor α [(382.3±114.4) ng/L vs (732.3±201.4) ng/L and (689.8±192 5) ng/L, P＜0. 05], neural-hormonal factors brain natriuretic peptide [(142.6±45.3) ng/L vs (422.3±113.6) ng/L and(393.7 ±103.3)ng/L, P＜0.01], endothelin-1 [(111.4 ±37.5)ng/L vs (193.5 ±54.3)ng/L and (201.0±72.1)ng/L,P＜0.05] and angiotensin Ⅱ[(189.7±65.2)μg/L vs (538.3 ± 135.2) μg/L and ( 525.5±144.1)μg/L, P＜0.01] were also significantly decreased in HF + SERCA2a group compared with HF/HF + EGFP groups. The apoptotic index [(12.71±4.11)% vs(23.22±7.23) % and (24.31±6.38)%, P＜0.05], protein levels of GRP78 (1.27±0.33 vs 3.23±1.14 and 4.18±1.13, P＜0.05)and protein level ratios of cleaved caspase-12 to total caspase-12[(4.62±1.93)% vs (9.71±2.70)% and (10.14±2.81)%, P＜0.05] were also significantly reduced in the ischemic myocardium of HF+SERCA2a group compared with the HF/HF + EGFP groups. Conclusion Overexpression of SERCA2a significantly improved cardiac systolic and diastolic function in this HF model partly through attenuation of ER stress related myocardial apoptosis, suggesting its therapeutic potential for CM1 related heart failure.     

过表达肌浆网钙ATP酶治疗实验性慢性缺血性心力衰竭

Objective Chronic myocardial ischemia (CMI) has become the most importat cause of heart failure (HF) all over the world. The aim of the current study was to investigate the effects of Sarcoendoplasmic reticulum calcium ATPaee 2a (SERCA2a) gene transfer on cardiac function and endoplasmic reticulum stress (ERS) associated myocardial apoptosis in a minipig HF animal model induced by CMI. Methods HF was induced in minipigs by implantation of ameroid constrictor in the initial segment of left anterior descending (LAD) branch of coronary artery. After confirmation of myocardial perfusion defects and cardiac function impairment by myocardial perfusion imaging and echocardiography, animals were divided into 4 groups (n =4 each): HF group, HF + enhanced green fluorescent protein (EGFP) group,HF + SERCA2a group, and shamed animals as control group. A total amount of 1×1012 v.g. Of rAAV1EGFP or rAAV1-SERCA2a were injected intramyocardially to each animal of HF + EGFP and HF +SERCA2a groups. Sixty days after gene transfer, protein level and activity of SERCA2a were examined,cardiac functions and changes of serum inflammatory and neuro-hormonal factors were determined. Apoptotic index of the ischemic myocardium, protein levels of ER stress marker glucose regulated protein 78 ( GRP 78) and ER stress specific apoptotic marker caspase-12 were also assayed. Results At the study end,echocardiographic and hemodynamic measurements indicated a significant improvement of both cardiac systolic and diastolic function in HF + SERCA2a group compared with HF/HF + EGFP groups [LVEF (60.2±8.6)%vs (44.2±7.1)% and (46.8±6.7)%, Ev/Ay 1.28±0.24 vs 0.77 ±0.17 and 0.80±0.21, +dp/dtmax(2713.9 ±434.0) mm Hg/s ( 1 mm Hg =0.133 kPa) vs (1892.3 ±434.2) mm Hg/s and (1931.2±397.4)mm Hg/s, -dp/dtmax (1422.1±334.4) mm Hg/s vs (848.3±308.3) mm Hg/s and (849.5±278.3)mm Hg/s, P＜0.05], along with increase in both SERCA2a protein level (1.13±0.26 vs 0.73 ±0.17 and 0.64±0.18, P＜0.05) and activity [(16.2±5.5) IU/ml vs (7.9±3.1) IU/ml and (7.5 ±2.8)IU/ml, P ＜0.05] compared with HF/HF + EGFP groups. Serum concentrations of inflammatory factor tumor necrotic factor α [(382.3±114.4) ng/L vs (732.3±201.4) ng/L and (689.8±192 5) ng/L, P＜0. 05], neural-hormonal factors brain natriuretic peptide [(142.6±45.3) ng/L vs (422.3±113.6) ng/L and(393.7 ±103.3)ng/L, P＜0.01], endothelin-1 [(111.4 ±37.5)ng/L vs (193.5 ±54.3)ng/L and (201.0±72.1)ng/L,P＜0.05] and angiotensin Ⅱ[(189.7±65.2)μg/L vs (538.3 ± 135.2) μg/L and ( 525.5±144.1)μg/L, P＜0.01] were also significantly decreased in HF + SERCA2a group compared with HF/HF + EGFP groups. The apoptotic index [(12.71±4.11)% vs(23.22±7.23) % and (24.31±6.38)%, P＜0.05], protein levels of GRP78 (1.27±0.33 vs 3.23±1.14 and 4.18±1.13, P＜0.05)and protein level ratios of cleaved caspase-12 to total caspase-12[(4.62±1.93)% vs (9.71±2.70)% and (10.14±2.81)%, P＜0.05] were also significantly reduced in the ischemic myocardium of HF+SERCA2a group compared with the HF/HF + EGFP groups. Conclusion Overexpression of SERCA2a significantly improved cardiac systolic and diastolic function in this HF model partly through attenuation of ER stress related myocardial apoptosis, suggesting its therapeutic potential for CM1 related heart failure.     

Ameliorated stress related proteins are associated with improved cardiac function by sarcoplasmic reticulum calcium ATPase gene transfer in heart failure

Background Previous studies showed that overexpression of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) in a variety of heart failure (HF) models was associated with greatly enhanced cardiac performance. However, it still undefined the effect of SERCA2a overexpression on the systemic inflammatory response and neuro-hormonal factors. Methods A rapid right ventricular pacing model of experimental HF was used in beagles. Then the animals underwent recombinant adeno-associated virus 1 (rAAV1) mediated gene transfection by direct intra-myocardium injection. HF animals were randomized to receive the SERCA2a gene, enhanced green fluorescent protein (control) gene, or equivalent phosphate buffered saline. Thirty days after gene delivery, the cardiac function was evaluated by echocardiographic testing. The protein level of SERCA2a was measured by western blotting. The proteomic analysis of left ventricular (LV) sample was determined using two-dimensional (2-D) gel electrophoresis and MALDI-TOF-MS. The serum levels of the systemic inflammatory and neuro-hormonal factors were assayed using radioimmunoassay kits. Results The cardiac function improved after SERCA- 2a gene transfer due to the significantly increased SERCA2a protein level. Beagles treated with SERCA2a had significantly decreased serum levels of the inflammatory markers (interleukin-6 and tumor necrosis factor-α) and neuro-hormonal factors (brain natriuretic peptide, endothelin-1 and angiotensin Ⅱ) compared with HF animals. The myocardial proteomic analysis showed that haptoglobin heavy chain, heat shock protein (alpha-crystallin-related, B6) were down-regulated, and galectin-1 was up-regulated in SERCA2a group compared with HF group, companied by up-regulated contractile proteins and NADH dehydrogenase. Conclusions These findings demonstrate that regional intramyocardial injections of rAAV1-SERCA2a vectors may improve global LV function, correlating with reverse activation of the systemic inflammatory, excessive neuroendocrine factors and the stress-associated myocardial proteins, suggesting that the beneficial effects of SERCA2a gene transfer may involve the attenuation of stress-associated reaction.     

非小细胞肺癌患者呼出气冷凝液中p53蛋白检测的临床意义

目的 研究非小细胞肺癌(NSCLC)患者呼出气冷凝液(EBC)中p53蛋白检测的临床意义.方法 收集98例NSCLC患者的EBC和血浆,应用双抗体夹心ABC-ELISA法检测EBC和血浆中p53蛋白表达水平,并与98名健康对照者测定值比较.用免疫组化法检测98例NSCLC患者手术切除标本癌组织中p53蛋白表达.比较肺癌组中不同分型、分期、病理类型、肿瘤大小以及有无淋巴结转移、吸烟史者EBC和血浆中p53蛋白水平和癌组织p53蛋白阳性表达率.应用 ROC曲线分析肺癌组血浆及EBC的p53蛋白诊断肺癌的特异性及敏感性.结果 ①肺癌组EBC中p53蛋白测定值高于健康对照组[(233.99±7.91)ng/L vs(130.26±4.73)ng/L,P＜0.01];肺癌组血浆p53蛋白测定值高于健康对照组[(292.58±8.79)ng/L vs(141.66±3.33)ng/L,P＜0.01].②肺癌组中央型患者EBC中p53蛋白测定值高于周围型患者[(248.22±8.58)ng/L vs(215.78±6.61)ng/L,P＜0.05].③免疫组化阳性组EBC中p53蛋白测定值高于阴性组「(249.77±8.07)ng/L vs(216.86±7.44)ng/L,P＜0.05].④肺癌组中吸烟者血浆p53蛋白测定值高于无吸烟者[(310.18±9.04)ng/L vs(254.55±6.91)ng/L,P＜0.01].⑤癌组织p53蛋白阳性表达率为47.96%(47/98).⑥血浆p53蛋白对于肺癌的诊断的敏感性为95.90%.特异性为90.04%;EBC p53蛋白埘于肺癌的诊断的敏感性为92.90%,特异性为79.59%;肺癌患者p53蛋白诊断最佳参考临界值血浆为175.68 ng/L,EBC为166.26 ng/L.结论 NSCLC患者中EBC p53蛋白的检测有助于肺癌的诊断.

Abstract：

Objective To study the clinical significance of the detection of p53 protein in exhaled breath condensate (EBC) of patients with non-small cell lung cancer (NSCLC). Methods EBC and plasma of 98 patients with NSCLC were collected,p53 protein expression in EBC and plasma was detected by enzyme-linked immunosorbent assay,and the data were compared with those of 98 healthy controls. p53 protein expression in cancer tissue of 98 patients with NSCLC was detected by immunohistochemistry. p53 protein expression in EBC and plasma and positive expression rate of p53 protein in cancer tissue were compared among patients with different lung cancer type,stage,histologic type,tumor size,and lymph node metastasis,smoking history. The specificity and sensitivity of diagnosis of p53 protein in patients with NSCLC were analyzed by ROC curve. Results ① The level of p53 protein in EBC of patients with NSCLC was significantly higher than that in healthy control group [(233.99±7.91) ng/L vs ( 130. 26 ± 4. 73) ng/L,P ＜0. 01]. The level of p53 protein in serum of patients with NSCI.C was significantly higher than that in healthy control group [(292. 58 ± 8. 79) ng/L vs (141. 66±3. 33) ng/L,P ＜0. 01]. ② The level of p53 protein in EBC of patients with central lung cancer was higher than that in patients with peripheral lung cancer [(248. 22 ± 8. 58) ng/L vs (215. 78 ± 6.61) ng/L,P＜0. 01]. ③The level of p53 protein in EBC of patients with positive immunostaining group was higher than that in negative group [(249.77 ± 8.07) ng/L vs (216.86 ± 7.44) ng/L,P ＜ 0. 05]. ④The level of p53 protein in serum of smokers was significantly higher than that in non-smokers [(310.18 ± 9.04) ng/L vs (254. 55 ± 6. 91) ng/L,P ＜0. 01]. ⑤The positive expression rate of p53 protein in cancer tissue was 47. 96% (47/98). ⑥The sensitivity and specificity of diagnosis of p53 protein were 95. 90% and 90. 04% in plasma,and those were 92. 90% and 79. 59% in EBC. The cut off values of p53 protein were respectively 175. 68 ng/L and 166. 26 ng/L in EBC and serum. Conclusions The detection of p53 protein in EBC of patients with NSCLC is helpful for the diagnosis of lung cancer.     

非小细胞肺癌患者呼出气冷凝液中p53蛋白检测的临床意义

Objective To study the clinical significance of the detection of p53 protein in exhaled breath condensate (EBC) of patients with non-small cell lung cancer (NSCLC). Methods EBC and plasma of 98 patients with NSCLC were collected,p53 protein expression in EBC and plasma was detected by enzyme-linked immunosorbent assay,and the data were compared with those of 98 healthy controls. p53 protein expression in cancer tissue of 98 patients with NSCLC was detected by immunohistochemistry. p53 protein expression in EBC and plasma and positive expression rate of p53 protein in cancer tissue were compared among patients with different lung cancer type,stage,histologic type,tumor size,and lymph node metastasis,smoking history. The specificity and sensitivity of diagnosis of p53 protein in patients with NSCLC were analyzed by ROC curve. Results ① The level of p53 protein in EBC of patients with NSCLC was significantly higher than that in healthy control group [(233.99±7.91) ng/L vs ( 130. 26 ± 4. 73) ng/L,P ＜0. 01]. The level of p53 protein in serum of patients with NSCI.C was significantly higher than that in healthy control group [(292. 58 ± 8. 79) ng/L vs (141. 66±3. 33) ng/L,P ＜0. 01]. ② The level of p53 protein in EBC of patients with central lung cancer was higher than that in patients with peripheral lung cancer [(248. 22 ± 8. 58) ng/L vs (215. 78 ± 6.61) ng/L,P＜0. 01]. ③The level of p53 protein in EBC of patients with positive immunostaining group was higher than that in negative group [(249.77 ± 8.07) ng/L vs (216.86 ± 7.44) ng/L,P ＜ 0. 05]. ④The level of p53 protein in serum of smokers was significantly higher than that in non-smokers [(310.18 ± 9.04) ng/L vs (254. 55 ± 6. 91) ng/L,P ＜0. 01]. ⑤The positive expression rate of p53 protein in cancer tissue was 47. 96% (47/98). ⑥The sensitivity and specificity of diagnosis of p53 protein were 95. 90% and 90. 04% in plasma,and those were 92. 90% and 79. 59% in EBC. The cut off values of p53 protein were respectively 175. 68 ng/L and 166. 26 ng/L in EBC and serum. Conclusions The detection of p53 protein in EBC of patients with NSCLC is helpful for the diagnosis of lung cancer.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

心房颤动对不同心功能分级的患者血浆脑钠肽水平的影响

Objective To assess the effect of atrial fibriUation (AF) on plasma levels of NT-proBNP in patients with different cardiac functions. Methods One hundred and ninty-one patients with chronic heart failure (CHF) were divided into two groups: minor CHF group (NYHA Ⅰ/Ⅱ class) and sever CHF group (NYHA Ⅲ/Ⅳ class). In addition,84 patients without HF (non-HF group) were enrolled as control The plas-ma NT-proBNP were assayed and the effect of AF on the NT-proBNP levels was analyzed to determine inde-pendent of NT-proBNP levels in 3 groups. Results Patients with AF in non-HF had higher NT-proBNP levels than those with sinus rhythm (SR) [(2.95 ±0.41) vs (2.21±0.44) ng/L, P < 0.01], and multi-variables regression demonstrated that age, AF and left atrial diameter (LAD) were independent determinants of NT-proBNP levels (P <0.001). NT-proBNP levels in minor CHF were also higher in patients with AF than that in patients with SR [(3.26±0.40) ng/L vs (2.98±0.54) ng/L, P < 0.05] ; AF, LAD, left ventricular end-systolic dimension (LVESD) and left vontric-ular eject fraction (LVEF) were the independent factors of NT-proBNP levels (P < 0.05). However, there was no difference of NT-proBNP levels between patients with AF and patients with SR [(3.59±0.52) ng/L vs (3.56±0.55) ng/L,P =0.73] ; while age and LVEF were in-dependent factors (P < 0.05). In patients with LVEF < 0.40, AF had not significant affect on NT-proBNP lev-els [AF vs SR: (3.70±0.60) ng/L vs (3.46±0.56) ng/L,P >0.10]; however,AF patients with LVEF≥ 0.40, NT-proBNP levels were increased [AF vs SR: (3.08 ±0.57) ng/L vs (2.67±0.73) ng/L, P < 0.001]. Conclusion The effect of AF on plasma NT-proBNP was related with cardiac functions: in AF pa-tients without or with minor cardiac dysfunction (NYHA Ⅰ /Ⅱ class or LVEF≥0.40) ,NT-proBNP increased; in AF patients with sever cardiac dysfunction (NYHA Ⅲ/Ⅳ class or LVEF < 0.40), NT-proBNP had no sig-nificant changes.     

肌浆网钙ATP酶基因转导对慢性心力衰竭犬心肌蛋白质组影响的初步研究

目的 分析心肌肌浆网Ca2+-ATP酶(sarcoplasmic reticulum Ca2+ ATPase 2a,SERCA2a)基因转导对慢性心力衰竭(HF)犬心肌蛋白质组的影响,探讨SERCA2a基因转导改善心功能的机制.方法 快速右心室起搏建立HF犬模型并随机分为HF组、HF+绿色荧光蛋白(enhanced green fluorescent pmtein,EGFP)组、HF+SERCA2a组.后两组分别向心肌内注射携带EGFP和SERCA2a基因的rAAV载体.于基因转导30 d时停止起搏后进行超声心动图和血流动力学检查并制备心室肌双向电泳蛋白样品和心肌双向电泳图谱,图像分析软件分析蛋白表达差异点,MALDI-TOF-MS数据库搜索鉴定蛋白质.结果 基因转导30 d时,HF+SERCA2a组犬的症状、超声心动图和血流动力学指标与HF+EGFP组相比有显著好转(P＜0.05);与对照组相比差异无统计学意义(P＞0.05).挑选SERCA2a基因转导后表达量发生明显改变的10个蛋白点进行分析,经质谱鉴定分别为心肌收缩相关蛋白、线粒体能量代谢酶类和应激相关蛋白.结论 以rAAV为载体介导SERCA2a基因转导能够改善HF犬心脏的收缩和舒张功能,其可能的机制是恢复了心肌收缩相关蛋白正常表型或正常表达量,增加了心肌能量的产生,改变了应激相关蛋白的表达.     

缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性的影响

目的 比较缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性及一氧化氮、内皮素的影响.方法选取61例2、3级老年高血压患者,随机分为两组,分别给予缬沙坦+氨氯地平或缬沙坦+氢氯噻嗪行降压治疗,观察入选时、治疗第8周和第16周各种相关指示的变化.人选时检测血脂、空腹血糖、血尿酸,试验各个阶段监测24 h动态血压,检测血浆一氧化氮、内皮素水平.结果在患者入选时、治疗第8周和第16周三个时间点,缬沙坦+氨氯地平组和缬沙坦+氢氯噻嗪组24 h血压及白昼血压比较差异无统计学意义.治疗第16周,缬沙坦+氨氯地平组晨峰收缩压较缬沙坦+氢氯嚷嗪组明显降低[(22.6±8.8)mm Hg(1 mm Hg=0.133 kPa)比(26.3±13.7)mm Hg,P＜0.05];缬沙坦+氨氯地平组及缬沙坦+氢氯噻嗪组24 h收缩压变异性(SBPV)进行性降低[缬沙坦+氨氯地平组:(12.5±2.8)mm Hg比(10.2 ±2.2)mm Hg比(8.8±1.6)mm Hg,P＜0.01;缬沙坦±氢氯噻嗪组:(12.5±2.5)mmHg比(10.7±2.2)mm Hg比(9.6±2.0)mmHg,P＜0.01],缬沙坦+氨氯地平组及缬沙坦+氢氯噻嗪组白昼SBPV明显降低[缬沙坦+氨氯地平组:(12.2±3.0)mm Hg比(10.1±2.3)mm Hg比(8.4±1.9)mm Hg,P＜0.01;缬沙坦+氢氯噻嗪组:(11.8±2.7)mm Hg比(10.4±1.9)mm Hg比(9.6±2.2)mm Hg,P＜0.01],缬沙坦+氨氯地平组24 h舒张压变异性(DBPV)显著降低[(15.5±3.4)mm Hg比(13.0±3.5)mm Hg比(12.3±2.5)mm Hg,P＜0.01],缬沙坦+氢氯噻嗪组24 h DBPV无显著性变化;缬沙坦+氨氯地平组第16周白昼SBPV低于缬沙坦+氢氯噻嗪组[(8.4±1.9)mm Hg比(9.6 ±2.2)mm Hg,p＜0.05],缬沙坦+氨氯地平第8周、第16周的24 h DBPV、白昼DBPV低于缬沙坦+氢氯噻嗪组(P ＜0.01～0.05);缬沙坦+氨氯地平组一氧化氮进行性升高[(27.3±13.6)μmol/L比(47.2±16.3)μmol/L比(69.5±18.9)μmol/L,P＜0.01]、内皮素进行性降低[(45.3±8.0)ng/L比(37.4±3.9)ng/L比(34.2±4.4)ng/L,P＜0.01];缬沙坦+氢氯噻嗪组一氧化氮进行性升高[(33.5±13.9)μmol/L 比(49.7±21.9)μmol/L比(66.7 ±24.7)μmol/L,P＜0.01]、内皮素显著降低[(46.6±10.4)ng/L比(37.0±5.4)ng/L比(36.1±8.2)ng/L,P＜0.01].治疗第8周,缬沙坦+氨氯地平组收缩压变异性的降幅与一氧化氮的升幅有相关性(r =0.401,P=0.025).结论缬沙坦联合氨氯地平或氢氯噻嗪均能降低老年高血压患者血压变异性、改善血管内皮功能,缬沙坦联合氨氯地平可能更适合于老年高血压患者.     

联合降压对中青年女性高血压病患者性功能的影响

目的 探讨以非洛地平为基础的联合降压方案在降压达标的基础上对中青年女性高血压病患者性功能的影响.方法 研究采用前瞻性、随机、平行、对照、开放、固定治疗的设计方案.选择2008-2009年在兰州大学第二医院就诊的中青年(年龄18～60岁)女性1～2级高血压病患者99例,随机分2组:非洛地平缓释片5 mg/d+厄贝沙坦片150 mg/d(F+I组,n=49),非洛地平缓释片5 mg/d+琥珀酸美托洛尔片47.5 mg/d(F+M组,n=50).以美国女性性功能指数量表(FSFI)进行问卷调查并检测血清雌二醇和总睾酮的含量,随访24周.FSFI总分以小于25.5定义为性功能障碍,以血压＜140/90 mm Hg(1 mm Hg=0.133 kPa)为达标.结果 F+I组与F+M组治疗第4、8、12周和第24周血压达标率分别为42.9%比62.0%、89.8%比90.0%、93.9%比94.0%和98.0%比96.0%,两组之间比较差异均无统计学意义(均P＞0.05).绝经前与绝经后患者在F+I组治疗后性欲指数和性唤起功能指数均升高(P分别＜0.05或＜0.01),雌二醇水平升高[绝经前:(50.3±37.4)pg/L比(54.4±10.8)pg/L,绝经后:(18.4±2.9)pg/L比(20.2±3.1)pg/L,P分别＜0.05或＜0.01],睾酮水平下降[绝经前:(722.8±277.1)ng/L比(650.0±156.0)ng/L,绝经后:(841.2±279.3)ng/L比(761.9±197.8)ng/L,P分别＜0.05或＜0.01];在F+M组治疗后性欲指数和阴道湿润度指数均降低(均P＜0.01),雌二醇水平降低[绝经前:(57.4±9.7)pg/L比(51.1±12.1)pg/L,绝经后:(19.8±2.3)pg/L比(17.8±3.3)pg/L,均P＜0.01],睾酮水平升高[绝经前:(775.6±217.8)ng/L比(886.0±186.4)ng/L,绝经后:(812.5±311.3)ng/L比(914.4±300.2)ng/L,均P＜0.01].高血压组FSFI总分与年龄和收缩压水平均呈负相关(均P＜0.01).结论 非洛地平缓释片与厄贝沙坦片或琥珀酸美托洛尔片联合降压达标率相同.前者可以在一定程度改善女性高血压病患者性功能.     

缬沙坦对心力衰竭家兔钙调蛋白依赖性蛋白激酶Ⅱ的影响

目的 探讨家兔慢性心力衰竭(心衰)时心肌钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)蛋白表达及活性的改变及血管紧张素Ⅱ受体拮抗剂缬沙坦长期干预的意义.方法 27只家兔随机分为3组,假手术组、心衰组和缬沙坦组各9只,通过超容量负荷联合压力负荷建立家兔心衰模型,于术后7周观察左心室结构、血液动力学的变化及CaMK Ⅱ的表达和活性的改变.结果 与假手术组比较,心衰组左室重量指数(LVMI)、左窒舒张末压显著升高(P＜0.05),左室短轴缩短率及左室射血分数明显降低(P＜0.05);与心衰组比较,缬沙坦组左室重量指数、左室舒张未压显著降低(P＜0.05),左室短轴缩短率及左室射血分数明显升高(P＜0.05);心衰组CaMK Ⅱ蛋白表达及活性显著高于假手术组(P＜0.05);缬沙坦组CaMKⅡ蛋白表达及活性显著低于心衰组(P＜0.05).结论 缬沙坦长期干预心衰,能够改善心脏舒缩功能,可能与其降低CaMK Ⅱ蛋白表达及活性有关.     

高原心脏病心功能指数与B型利钠肽相关研究

目的 通过观察高原心脏病心力衰竭患者心功能综合指数(Tei)和外周血N末端B型利钠肽前体(NT-proBNP)水平,探讨右室Tei指数、NT-proBNP在高原心脏病中的诊断价值.方法 对2008-2010年在解放军第二十二医院心内科住院的34例高原心脏病患者进行超声指标Tei指数和NT-proBNP水平测定,并进行相关性比较.结果 根据超声心动图征象将高原心脏病患者分为A、B两组,A组与健康对照组(C组)相比,肺动脉收缩压[86.6 mm Hg比9.7 mm Hg(1 mum Hg =0.133kPa)]、右室Tei指数(0.90比0.33)均显著增高(P＜0.05);B组C组相比,肺动脉收缩压(57.1比9.72) mm Hg、右室Tei指数(0.78比0.33)显著增高(P＜0.05);A、B两组患者外周血NT-proBNP水平分别为(1246.8±512.6)ng/L、( 637.3±351.3) ng/L,均显著高于C组(98.6±21.7) ng/L水平,P＜0.05.结论 右心室Tei指数和NT-proBNP浓度是反映右心整体功能的较敏感指标,两者对于诊断高原心脏病具有一定的临床意义.     

牙周基础治疗对老年牙周疾病患者血清炎性标记物的影响

目的 观察患有牙周病的老年人经过牙周基础治疗后,其冠心病相关血清炎性标记物的变化.方法 选择老年牙周病患者52例,记录其探诊深度(probing depth,PD)、附着水平(attachment level AL)、C-反应蛋白(C-reactive protein,CRP)和白细胞介素-6(interleukin-6 IL-6)水平.牙周基础治疗后3个月、6个月再次检查牙周临床指标,测定CRP和IL-6水平,比较治疗前后各项指标的变化.结果 治疗后6个月,PD和AL值分别为(5.9±1.1)mm和(6.8±1.0)mm,与治疗前[分别为(7.5±1.2)mm和(8.4±1.1)mm]比较,差异有统计学意义(均P＜0.05).CRP和IL-6分别为(1.5±0.2)mg/L和(1.6±0.5)ng/L,与治疗前[分别为(2.0±0.3)mg/L和(1.9±0.4)mg/L]比较,差异有统计学意义(分别为P＜0.01,P＜0.05).结论 牙周基础治疗能降低老年牙周疾病患者冠心病相关血清炎性标记物CRP和IL-6的水平.

Abstract：

Objective To ascertain serum inflammatory markers could be modified following treatment of periodontal disease in elderly patients. Methods The probing depth (PD), clinical attachment level (AL), C-reactive protein (CRP), interleukin-6 (IL-6) were determined. And then fifty-two elderly periodontitis patients underwent a standard phase of non-surgical periodontitis treatment (consisting of oral hygiene instructions and subgingival scaling and root planning). After three and six months, PD, AL, CRP and IL-6 were determined again and compared to the baseline. Results Six months after treatment, significant reductions in PD [(5.9±1.1) mm vs. (6.8±1.0) mm, P＜0.05], AL [(1.3±0.9) mm vs.(8.4±1.1) mm, P＜0.05], CRP [(1.5±0.2) mg/L vs. (2.0±0.3) mg/L, P＜0.01] and IL-6 [(1.6±0.5) ng/L vs. (1.9±0.4) ng/L, P＜0.05] were observed. Conclusions Treatment of chronic periodontitis can decrease the levels of serum inflammatory markers in elderly patients.     

骨髓间充质干细胞对大鼠梗死心肌胶原重构的双重调节作用

目的 探讨骨髓间充质干细胞(MSC)对梗死心肌胶原重构的调节作用。方法 采用结扎冠状动脉前降支的方法复制大鼠心肌梗死(MI)模型,随机分为假手术组（仅穿线不结扎冠状动脉,n=8）、MI+ PBS组（结扎冠状动脉+心肌注射PBS溶液,n=8）和MI+ MSC组（结扎冠状动脉+心肌注射MSC,n=8）。通过心脏超声检查、血液动力学检查和组织学染色方法分别检测左心室射血分数(LVEF)、短轴缩短率(FS)、左心室收缩末压力(LVSP)、左心室舒张末压力(LVEDP)、左心室压最大升降速率（±dp/dtmax）、心肌梗死面积和梗死扩张指数等指标,评价MSC对大鼠心功能及心室重构的影响。同时采用免疫组化、RT-PCR、Western blot等方法,测量胶原蛋白表达情况。结果 (1)MI大鼠心室重构和心脏功能指标的检测结果：MI+ MSC组大鼠心肌梗死面积显著小于MI+ PBS组[(38.27±2.70)％比(46.20±3.17)％,t=5.386,P＜0.001],FS显著高于MI+ PBS组[(29.98±4.50)％比(23.43 ±3.34)％,t=-3.305,P=0.005],LVSP显著高于MI+ PBS组[(113.63±10.81)mm Hg(1 mm Hg=0.133 kPa)比（99.25±16.76）mm Hg,P＜0.05],LVEDP显著低于MI+PBS组[(12.10±4.28) mm Hg比(20.08±4.26) mm Hg,P＜0.05],+dp/dtmax显著高于MI+ PBS组[（4616.63±363.34）mum Hg/s比(3912.75±248.79) mm Hg/s,P＜0.05],- dp/dtmax显著高于MI+ PBS组[(4254.63±324.34) mm Hg/s比（3530.88±309.71）mm Hg/s,P＜0.05]。(2)Ⅰ型和Ⅲ型胶原蛋白表达水平的检测结果：MI+ MSC组大鼠梗死区Ⅰ型和Ⅲ型胶原蛋白表达均显著高于MI+ PBS组,而非梗死区Ⅰ型和Ⅲ型胶原蛋白表达均显著低于MI+ PBS组（P均＜0.05）。结论 MSC通过促进MI大鼠梗死区胶原蛋白修复性合成,减少非梗死区胶原蛋白沉积,从而抑制心室重构,改善心脏功能。     

腺相关病毒介导心肌肌浆网Ca2+-ATPase 2a基因转导治疗大鼠慢性心力衰竭

目的 研究腺相关病毒为载体的心肌肌浆网Ca^2＋ -ATPase 2a（sarcoplasmic reticulum Ca^2＋ -ATPase,SERCA2a）基因转导对慢性心力衰竭（HF）大鼠的治疗作用,并探讨其多种可能的机理.方法 采用腹主动脉缩窄术建立HF大鼠模型,应用经腹心包腔内注射术分别将生理盐水、携带eGFP基因和携带SERCA2a基因的重组腺相关病毒导入HF、HF＋EGFP和HF＋SERCA2a组大鼠心脏.于导入30天,检测各组大鼠的心脏功能、SERCA2a蛋白表达和活性;比较HF组和HF＋SERCA2a组大鼠心肌蛋白质组表达的差异;检测各组大鼠心肌肌球蛋白重链（MHC）亚型的表达.结果 HF大鼠心脏内转导入SERCA2a基因30天,心脏收缩和舒张功能达到对照组大鼠水平,并且HF＋SERCA2a组左室重/体重比值显著降低;SERCA2a蛋白表达和活性明显升高至对照组大鼠水平;多种能量代谢酶表达明显增加;α-MHC、β-MHC的表达以及α-MHC/β-MHC恢复至对照组大鼠水平.结论 以重组腺相关病毒2作为载体,SERCA2a基因转导可以增强衰竭心脏的SERCA2a功能,增加心脏能量代谢,纠正MHC亚型的异常表达;在临床方面表现为显著改善心脏收缩和舒张功能,可能能够减轻心脏肥厚等病理性结构改变.     

携带人B型利钠肽基因重组腺病毒对慢性心力衰竭大鼠心功能的影响

目的 观察外源基因人B型利钠肽对慢性心力衰竭(心衰)大鼠心功能的影响.方法 30只入选心衰大鼠,随机分为携带人B型利钠肽基因重组腺病毒组(Ad-hBNP组)、重组空白腺病毒组(Ad-Track组)、生理盐水组(NS组),另设不予任何治疗的假手术组作为对照;分别经腹腔注射予以相应治疗,每周1次,共4周.4周后实验动物行超声心动图、血流动力学检测,酶联免疫吸附试验检测血清外源基因人B型利钠肽水平,全心质量指数检测.结果 间断Ad-hBNP治疗后,Ad-hBNP组心衰大鼠室间隔厚度、左室后壁厚度、左室舒张末径、左室收缩末径[(2.34±0.29)mm、(2.28±0.18)mm、(6.50±0.42)mm、(3.54±0.59)mm]显著低于Ad-Track组[(2.71±0.35)mm、(3.02±0.85)mm、(7.71±0.83)mm、(4.72±0.80)mm,均为P＜0.05]和NS组[(2.78±0.23)mm、(2.83±0.53)mm、(7.34±0.97)mm、(4.55±0.77)mm,均为P＜0.05],而左室射血分数、左室短轴缩短率[(79.27±7.01)%、(43.38±6.73)%]显著高于Ad-Track组[(70.85±4.81)%、(35.72±3.68)%,均为P＜0.01]和NS组[(69.67±6.90)%、(34.91±5.10)%,均为P＜0.01].Ad-hBNP组与Ad-Track组和NS组比较:心率显著降低,左室收缩压显著升高[为(131.79±15.76)mm Hg(1 mm Hg=0.133 kPa)、(112.99±32.35)mm Hg、(117.13±15.26)mm Hg],左室内压最大上升速率显著升高[分别为(5037.20±430.41)mm Hg/s、(4217.40±1354.15)mm Hg/s、(4310.50±1293.97)mm Hg/s;P＜0.05];左室内压最大下降速率显著升高[分别为(-4382.00±1304.79)mm Hg/s、(-3725.00±791.34)mm Hg/s、(-3890.00±1043.73)mm Hg/s,均为P＜0.05];左室舒张末压降低[分别为(-4.24±4.00)mm Hg、(21.99±6.80)mm Hg、(18.00±12.25)mm Hg,均为P＜0.01];心脏质量及全心质量指数均降低.结论 间断给予Ad-hBNP能够有效地改善心衰大鼠心脏结构和功能.

Abstract：

Objective To evaluate the therapeutic effect of hBNP on rats with chronic heart failure (CHF). Methods Thirty CHF rats defined by echocardiography at 12 weeks post abdominal aortic constriction were randomly divided into Ad-hBNP group (2. 5 × 1010 VP/ml NS Ad-hBNP 1 ml/week ×4,n = 14), Ad-Track group ( n = 8 ), placebo group ( NS, n = 8 ), 10 sham-operated rats served as control group. After 4 weeks treatment, cardiac function was evaluated by echocardiography and hemodynamic measurements. Heart weight (HW) and HW/body weight (BW) ratio were determined. Results IVS,LVPW, LVEDD and LVESD were significantly reduced in the Ad-hBNP group [(2. 34 ±0. 29)mm, (2. 28 ± 0. 18)mm, (6. 50 ±0. 42)mm, (3.54 ±0. 59) mm] than those in the Ad-Track group[(2. 71 ±0. 35) mm,(3.02 ±0.85)mm, (7.71 ±0.83)mm, (4.72 ±0.80)mm] and in the NS group [(2.78 ±0.23)mm,(2. 83 ± 0. 53 ) mm, (7. 34 ± 0. 97 ) mm, (4. 55 ± 0. 77 ) mm, all P ＜ 0. 05]. The LVEF and LVFS of the Ad-hBNP group [(79. 27 ±7.01 )%, (43.38 ±6. 73)%] were significantly higher than in the Ad-Track group[(70.85±4.81)%, (35.72 ±3.68)%] and in the NS group[(69.67 ±6.90)%, (34.91 ±5.10)%, all P ＜0. 01]. HR[(417.48 ±32. 57) beats/min, (446. 85 ±61.49) beats/min, P ＜0. 05;(440. 83 ±32. 18) beats/min , P ＜0. 05], LVEDP[( - 4. 24 ±4. 00) mm Hg( 1 mm Hg =0. 133 kPa);(21.99 ±6. 80) mm Hg, P ＜0. 01; ( 18.00 ± 12. 25)mm Hg, P＜0. 01] were significantly decreased and while LVSP[(131.79 ±15.76) mm Hg; (112.99 ±32.35) mm Hg, P＜0.05; (117.13 ±15.26)mmHg], +dP/dtmax[(5037.20 ±430.41) mm Hg/s; (4217.40 ± 1354. 15)mm Hg/s, P ＜0.05;(4310. 50 ± 1293.97 ) mm Hg/s, P ＜ 0. 05] and - dP/dtmax [( - 4382. 00 ± 1304. 79 ) mm Hg/s;(-3725.00±791.34) mm Hg/s, P ＜ 0.05; ( - 3890.00 ± 1043.73) mm Hg/s, P ＜ 0.05] were significantly increased in Ad-hBNP group than in Ad-Track group and NS group ( all P ＜ 0. 05 ). HW and HW/BW were also decreased in Ad-hBNP group than in the Ad-Track group and the NS group. Conclusion Exogenous hBNP improved the cardiac function and attenuated remodeling in CHF rats.     

丙氨酸转移酶升高的2型糖尿病患者伴有更多的心血管风险因素

根据血丙氨酸转氨酶(ALT)水平将4 509例2型糖尿病患者分为A组(n=449,ALT增高)和B组(n=4 060,ALT正常),ALT升高的患者为10%.与B组患者相比,A组患者相对年龄更轻[(48.5±11.3对55.7±11.4)岁,P＜0.01]、糖尿病病程更短[(36.8±45.0对56.2±58.8)个月,P＜0.01]、体重指数以及腰臀比更大[(27.7±3.9对25.8±3.4)kg/m2,P＜0.01;0.95±0.06对0.93±0.07,P＜0.01].两组之间的血压存在差别[收缩压(132±19对131±21)mm Hg,1 mm Hg=0.133 kPa,P=0.60;舒张压(78±10对75±10)mm Hg,P＜0.01].A组的空腹血糖[(9.04±2.91对8.63±3.05)mmol/L,P=0.008]、餐后血糖[(13.85±4.67对13.07±4.92)mmol/L,P=0.002]、HbA1C(8.11%±1.82%对7.74%±1.96%,P＜0.01)、空腹胰岛素[(10.59±7.31对7.97±7.18)mU/L,P＜0.01]和餐后胰岛素[(48.96±43.80对35.25±32.37)mU/L,P＜0.01]及稳态模型评估的胰岛素抵抗指数(HOMA-IR,4.11±2.85对3.00±2.92,P＜0.01)、甘油三酯[(2.77±2.50对2.19±2.99)mmoL/L,P＜0.01]明显增高,高密度脂蛋白胆固醇[HDL-C,(1.20±0.30对1.29±0.83)mmol/L,P=0.01]更低.Logistic回归分析说明,HbA1C、餐后胰岛素、HOMA-IR、尿酸和尿白蛋白与ALT水平正相关,HDL-C则为负相关.提示ALT增高的2型糖尿病患者发病年龄更轻,有更严重的胰岛素抵抗和更多的心血管危险因素.