GAO Hao,et al: Vasodilating Effect of BNP in Different Kind of Buffer Systems Research Mini-Review Article BNP 2~6 [5] 1.2 (recombinant human brain 1.

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1 高昊, 等 : BNP 在不同缓冲体系中的血管舒张功能评价 BNP 高昊, 刘利平, 马鑫, 陈蕴, 金坚 * ( ) : 为了明确能使人脑纳肽 (Brain Natriuretic Peptide) 保持活性的适用缓冲溶液条件, 采用常规离体血管灌流实验, 观察人脑纳肽的不同缓冲溶液对家兔离体兔胸主动脉血管片段舒张功能的影响研究发现, 在以柠檬酸 / 磷酸氢二钠为基质的缓冲液条件下,BNP 在 10-8 ~10-5 mol/l 浓度区间对家兔血管舒张均呈良好的剂量依赖关系, 而以醋酸 / 醋酸钠或磷酸氢二钾 / 磷酸二氢钾为基质的这两种缓冲液虽有一定的舒张效果, 但没有剂量依赖关系由此表明, 在合适的 ph 条件下 (4 或 5), 柠檬酸 / 磷酸氢二钠缓冲液具有作为改进 BNP 注射剂处方的潜在价值 : 人脑纳肽 ; 柠檬酸 / 磷酸氢二钠缓冲溶液 ; 离体血管灌流 ; 注射剂处方 :R 972 :A : (2013) Vasodilating Effect of BNP in Different Kind of Buffer Systems GAO Hao, LIU Li-ping, MA Xin, CHEN Yun, JIN Jian * (School of pharmaceutical Sciences,Jiangnan University,Wuxi ,China) Abstract: To investigate the vasodilating effect of BNP in different buffer solutions,rabbit thoracic aorta was rapidly dissected out and the effect of BNP on the tension of aortic rings was measured in an organ bath system. The results showed that BNP in Citric acid/na2hpo4 buffer caused a concentration-dependent relaxation. However,BNP in NaAc/HAC or K2HPO4/KH2PO4 buffer has vasodilating effect in dose -independent manner. The results indicate that BNP in Citric acid/ Na2HPO4 buffer could keep its vasodilating effect in a dose-dependent manner,implying that they may be effective in BNP formulation. Keywords: brain natriuretic peptide,citric acid/na 2 PO 4 buffer,isolated vascular perfusion, injectable prescription BNP RAAS -1 SNS [1] BNP [3], [2], [4] BNP BNP : : ( ) * : (1960 ) jinjian31@126.com 貕貚貤

2 GAO Hao,et al: Vasodilating Effect of BNP in Different Kind of Buffer Systems Research Mini-Review Article BNP 2~6 [5] 1.2 (recombinant human brain 离体血管的灌流实验 natriuretic peptide,rhbnp), Krebs FDA SFDA, 3~4 mm ,The Connor Group FDA ( ( ),medease ) 2.5 g6 μmol/ Connor L KCl KCl 20 min [6] 6 μmol/l, 10-8 ~10-5 mol/l BNP FDA, BNP, 10-5 mol/l :, [7] rhbnp, : ; = - 100% rhbnp, rhbnp ph 梯度缓冲液的配备 ph 4 BNP ( ±0.2) / BNP ( ) / ( ) BNP / ( )3 BNP ph 1.1 [8] 3 BNP ( :SPKMVQGSGCFGRKMDRI 斑马鱼体内试验 SSSSGLGCKVLRRH), 3 ml >99% Cys ( 3 ) ( 3 μl S ), 0.5 mg 8 mg 1.73 mg Na 2 HPO mg NaH 2 PO 4 9 mg NaCl, 160 μg/ml MS222( ) Krebs :NaCl 9.0 g KCl 0.42 g 28 CaCL g NaHCO 3 0.1~0.3 g 1.0~2.5 g (1 000 ml) 2~2.5 kg 37 4 ml Krebs 10 nl 2 h 貕貚貥 Journal of Food Science and Biotechnology Vol.32 No

3 高昊, 等 : BNP 在不同缓冲体系中的血管舒张功能评价 Table 1 1 Preparation of mother solution /(mol/l) ,BNP ph 4 5 /,, ph=5 /,BNP 10-7 mol/l ph=6 BNP (P>0.05) ph=6, ph BNP EC50 BNP 2 Table 2 Preparation of buffer ph v( ) v( ) v( ) v( ) v( ) v( ) 4.0± ± ± ± ± Table 3 Buffer capacity mol/l ~ 统计学方法 ± (x 軃 ±s) Graphpad Prism5 2.2 BNP / t,p< ph 1 Fig. 1 / / / 4 Table 4 4.0± ± ± ± ± BNP / Relationship between BNP in HAc/NaAc buffer concentration and relaxation effects on isolated vascular / EC50 95% EC50 and 95% Confidence Intervals of / buffer ph logec50 95% ~ ~ ~ , ph 6 7,BNP ; ph=8,bnp 2.1 BNP / ph=6,ph=7 1 /, ph,bnp BNP EC50 95%, 貕貚貦

4 GAO Hao,et al: Vasodilating Effect of BNP in Different Kind of Buffer Systems Research Mini-Review Article 2 BNP / ~40.79 Fig. 2 Relationship between BNP in K 2 HPO 4 /KH 2 PO 4 buffer concentration and relaxation effects oon ~ ~ isolated vascular 2.4 / EC50 95% Table 5 EC50 and 95% Confidence Intervals of K 2 HPO 4 / KH 2 PO 4 buffer BNP BNP ph logec50 95% ~ ~ ~ BNP / 3 6,BNP ph 4~6, BNP (50% vs 100%,50% vs 100%), 10-8 ~10-5 mol/l BNP 6 / EC50 95% Table 6 EC50 and 95% Confidence Intervals of Citric acid/na 2 HPO 4 buffer ph logec50 95% ~ ~ ~ BNP 给药前处理,, 4 4 Fig. 4 Zebra fish model 3 BNP Citric acid/na 2 HPO 4 Fig. 3 Relationship between BNP in Citric acid/na 2 HPO 4 buffer concentration and relaxation effects on isolated vascular 给药注射观察 BNP,pH 4 5, :BNP ph=4 ph=5 BNP ph=4 ph=5, 貕貚貧 Journal of Food Science and Biotechnology Vol.32 No

5 高昊, 等 : BNP 在不同缓冲体系中的血管舒张功能评价 Fig. 5 Fig. 6 5 ph=4.0 BNP 4 (100% vs 20%) Effect of BNP in ph=4.0 buffer in zebra fish model, 6 ph=5.0 BNP Effect of BNP in ph=5.0 buffer in zebra fish model, BNP Connor rhbnp,bnp BNP [10] BNP,,pH 5 6 BNP 3 2.5,BNP ph BNP, [9], BNP BNP, BNP ph, BNP BNP /,BNP, BNP, BNP, BNP : [ 1 ] Potter L R,Yoder A,Flora R,et al. Natriuretic peptides:their structures,receptors,physiologic functions and therapeutic applications[j]. Handb Exp Pharmacol,2009,191: [ 2 ] Alexander G Semenov,Karina R Seferian. Biochemistry of the human B-type natriuretic peptide precursor and molecular aspects of its processing[j]. Clinica Chimica Acta,2011,412: [ 3 ] Mark Oremus,Parminder S Raina. A systematic review of BNP as a predictor of prognosis in persons with coronary artery disease [J]. Clinical Biochemistry,2008,41: [ 4 ] Yunus Emiroglu,Ramazan Kargin. BNP levels in patients with long -term exposure to biomass fuel and its relation to right ventricular function[j]. Pulmonary Pharmacology & Therapeutics,2010,23: 貕貚貨

6 GAO Hao,et al: Vasodilating Effect of BNP in Different Kind of Buffer Systems Research Mini-Review Article [ 5 ] Lee C Y,Burnett J C. Natriuretic peptides and therapeutic applications[j]. Heart Fail Rev,2007,12: [ 6 ] Chen H H,Burnett J C. Clinical application of the natriuretic peptides in heart failure [J]. European Heart Journal Supplements,2006(8):E18-E25. [ 7 ]. C [J].,2001(2): WANG Yue-ming,Pei Jian-ming,Zhu Miao-zhang,et al. C-type natriuretic peptides of expanding blood vessel function and mechanism[j]. Chinese Journal of Applied physiology,2011(2): (in Chinese) [ 8 ]. [M]. :,1997. [ 9 ]. [J].,2010,45(5):5-6. XU guo-heng. Disulfide bond and protein structure[j]. Bulletin of Biology,2010,45(5):5-6.(in Chinese) [10]. B [J].,2011,24(4): GU Yi. The application process of B -type natriuretic peptide in chronic heart failure [J]. Chinese Journal of Clinical Research,2011,24(4): (in Chinese) ( ): 2013 : : : : : : : : swzpfh@163.com : ( ): :, : : : : : : : chai.yan@163.com; @163.com : ( ): :, : : : : : : hnzwxh@163.com : 貕貚販 Journal of Food Science and Biotechnology Vol.32 No

5-25袁宏钧.indd

5-25袁宏钧.indd 第 24 卷第 5 期 2015 年 5 月碘 131 doi:10.3978/j.issn.1005-6947.2015.05.005 http://dx.doi.org/10.3978/j.issn.1005-6947.2015.05.005 Chinese Journal of General Surgery, 2015, 24(5):643 647. Chinese Journal of