超长效氨氯地平皮下埋植制剂对自发性高血压大鼠肝、肾功能的影响

Effects of Super Long Effect Amlodipine Subcutaneous Implant on Liver and Kidney Function in Spontaneously Hypertensive Rats

【目的】探讨超长效氨氯地平皮下埋植制剂对自发性高血压大鼠(SHR)肝、肾功能的影响。【方法】将有机高分子聚合物聚己内酯合成缓释载体,加入氨氯地平原料药制成可皮下埋植的氨氯地平缓释制剂。将SHR随机分成模型对照组(MC组)、空白载体埋植组(BCE组)、氨氯地平溶液灌胃组(ASG组)、氨氯地平缓释制剂埋植组(ARI组),每组8只;正常对照组(NC组)为8只WKY大鼠。NC组及MC组SHR不予干预,将空白载体、氨氯地平缓释剂分别植入BCE及ARI组SHR的颈部背皮下,ASG组SHR予以氨氯地平溶液(0.45mg/kg)灌胃,干预12周。实验期间,定期测定大鼠体重、尾动脉血压,采集静脉血检测肝、肾功能。【结果】干预12周后,ASG组及ARI组SHR收缩压、舒张压及平均动脉压均低于MC组(P<0.01),与NC组比较差异无统计学意义(P>0.05)。与MC组及ASG组比较,ARI组SHR血清天门冬氨酸氨基转移酶(AST)降低,但差异无统计学意义(P=0.054);各组SHR血清血肌酐(Cr)均有所升高,但与NC组比较,差异无统计学意义(P>0.05)。【结论】皮下埋植超长效氨氯地平缓释制剂在平稳降低SHR血压的同时,对肝功能可能存在一定的保护作用,对肾功能的影响与口服药物无明显差别。

【Objective】To investigate the effect of subcutaneous implantation of super long-acting amlodipine on liver and renal function in spontaneously hypertensive rats(SHR).【Methods】Organic polymer polycaprolactone was synthesized into sustained-release carrier,and amlodipine sustained-release preparation which can be implanted subcutaneously was prepared by adding amlodipine raw material.SHR was randomly divided into model control group(MC group),blank carrier implantation group(BCE group),amlodipine solution gavage group(ASG group)and amlodipine sustained-release preparation implantation group(ARI group),with 8 rats in each group;The normal control group(NC group)was 8 WKY rats.SHR in the NC group and the MC group were not intervened.Blank carrier and amlodipine sustained-release agent were implanted into the cervical dorsal subcutaneous layer of SHR in the BCE group and the Ari group respectively.SHR in the ASG group was given amlodipine solution(0.45 mg/kg)by gavage for 12 weeks.During the experiment,the body weight and tail artery blood pressure of rats were measured regularly,and venous blood was collected to detect liver and kidney functions.【Results】After 12 weeks of intervention,the systolic blood pressure,diastolic blood pressure and mean arterial pressure of SHR in the ASG group and the ARI group were lower than those in the MC group(P<0.01),and there was no significant difference between the ASG group and the NC group(P>0.05).Compared with the MC group and the ASG group,the serum aspartate aminotransferase(AST)of SHR in the ARI group decreased,but the difference was not statistically significant(P=0.054);Serum creatinine(CR)in SHR increased in all groups,but there was no significant difference compared with the NC group(P>0.05).【Conclusion】Subcutaneous implantation of super long-acting amlodipine sustained-release preparation may have a protective effect on liver function while steadily reducing blood pressure in SHR,and its effect on renal function is not significantly different from that of oral drugs.