Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.
目的 确定利血平诱导大鼠低血压模型的适合剂量与时间。方法 60只雄性Wistar大鼠按照体重及收缩压水平进行分层,然后每层再按照随机数字表法分为对照组和5个不同剂量实验组,每组10只。对照组灌胃0.5%羧甲基纤维素钠溶液10 ml/kg,实验组灌胃利血平混悬液10 ml/kg,给药浓度分别为0.016、0.032、0.064、0.128、0.160 mg/kg,各组均每日灌胃2次。每日监测大鼠体重,分别于造模前和给药后1~6周末测量大鼠收缩压及心率变化。给药6周后,目内眦取血检测大鼠血清乳酸脱氢酶、肌酸激酶同工酶、谷丙转氨酶、谷草转氨酶、血肌酐及尿素氮水平,每组随机选取3只观察停药后大鼠收缩压变化情况,其余大鼠处死后测定脑内去甲肾上腺素及多巴胺水平。结果 与对照组比较,不同浓度利血平均可降低大鼠收缩压水平(F=28.492,P<0.001),收缩压下降幅度随药物浓度的增高而增加,第1周达到最低,随后稍有回升,给药3周后趋于稳定。其中0.016 mg/kg组大鼠收缩压水平自灌胃第5周开始与对照组比较差异均无统计学意义(P均>0.05);0.032、0.064、0.128、0.160 mg/kg组各时间点大鼠收缩压水平均显著低于对照组(P均<0.001),但4种不同给药浓度组间比较差异无统计学意义(P=0.204)。停药1周后,不同浓度利血平组大鼠收缩压均回升至基线水平,并维持稳定。各组间大鼠心率随时间的变化趋势一致,均呈现先增快后减慢的变化特点,相同时间点不同组间大鼠心率差异无统计学意义(F=0.922,P=0.475)。与对照组比较,不同浓度利血平组大鼠海马去甲肾上腺素含量(P均<0.001)及0.128 mg/kg(P=0.045)、0.160 mg/kg(P=0.042)组大鼠纹状体多巴胺水平显著降低,但不同浓度利血平组间比较差异无统计学意义(P=0.343,P=0.301)。不同浓度利血平组大鼠血清乳酸脱氢酶、肌酸激酶同工酶及尿素氮水平随利血平浓度增高而增加,其中0.160 mg/kg组乳酸脱氢酶(P=0.001)、肌酸激酶同工酶(P=0.020)、谷草转氨酶(P=0.007)及尿素氮(P=0.001)与对照组比较差异有统计学意义。结论 利血平灌胃可成功诱导大鼠低血压模型,其中利血平0.032 mg/kg、每日2次灌胃、连续3周为造模适宜条件,成模后需持续给药以维持大鼠稳定的低血压状态。.
Keywords: animal model; hypotension; reserpine.