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.

Improvement of cardiac function by recombinant adenovirus Ad-hBNP in rats with chronic heart failure

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.