金匮肾气丸对创伤后应激障碍综合征孕鼠子代行为遗传及多巴胺的影响

Impact of Jinkui Shenqi Pills on Behavioral Genetics and Dopamine of Offspring from Pregnant Rats with Posttraumatic Stress Disorder Syndrome

背景近年来,创伤后应激障碍综合征(PTSD)的发生率呈上升趋势。采用西医对PTSD进行治疗存在药物不良反应、疗效及疗程不确定性等诸多问题,对孕妇危害更大。目的观察金匮肾气丸对PTSD孕鼠子代生长发育、行为能力及血清多巴胺(DA)水平的影响。方法 2014年7月—2015年3月,采用随机数字表法将初次受孕的36只SD孕鼠分为空白组、PTSD组、中药组,每组各12只。妊娠中期,PTSD组和中药组孕鼠采用单程长时应激法进行创伤应激造模,造模后中药组给予金匮肾气丸饲料至分娩。子鼠出生后第5、15、25天测量身长、尾长以反映生长发育状况;第15天进行亮盒排便测试,第26天进行糖水消耗试验,以观察其行为能力;第30天抽取股动脉血,采用酶联免疫吸附试验法检测血清DA水平。结果不同处理方法、时间在子鼠身长和尾长上主效应显著(P<0.05),不同处理方法和时间在子鼠身长和尾长上存在交互作用(P<0.05)。PTSD组亮盒排便测试阳性率高于空白组和中药组,糖水偏嗜度低于空白组和中药组(P<0.05),中药组和空白组间差异无统计学意义(P>0.05)。PTSD组血清DA水平低于空白组和中药组(P<0.05),中药组和空白组间差异无统计学意义(P>0.05)。结论金匮肾气丸可纠正孕鼠PTSD导致的子代生长发育迟缓、行为异常、血清DA紊乱,其作用机制可能与先天补肾温阳、髓海充盈、脑神充养有关。

Background The incidence rate of post- traumatic stress disorder（ PTSD） syndrome has increased in recent years. Western medicine treatment of PTSD leads to adverse drug reactions,uncertainties of curative effect and treatment,and other problems that are especially harmful for pregnant women. Objective To observed the effect of Jinkui Shenqi pills on growth and development, behavior capacity, and serum dopamine（ DA） level of offspring from pregnant rats with post-traumatic stress disorder（ PTSD）. Methods From July 2014 to March 2015,36 pregnant rats were divided into： control group（ CG）,PTSD group（ PG）,and herbal group（ HG） by random number table method. There were 12 rats in each group. The pregnant metaphase rats in PG and HG were transformed to PTSD models via single- prolonged stress（ SPS）,which has been extensively applied in PTSD research. After the models were established,the rats in HG were given Jinkui Shenqi pills. The body and tail lengths of rats were measured 5,15,and 25 days after birth to observe growth and development status. Behavioral ability was evaluated by different behavioral tests at different times, including light box defecation test（ 15 days after birth） and saccharose consumption test（ 26 days after birth）. Femoral arterial blood of the offspring was sampled on the 30 days after birth,and serum dopamine level was detected by enzyme- linked immune sorbent assay（ ELISA）. Results There was significant effect on body length and tail length among different treatment ways and time（ P〈0. 05）,there was interaction on body length and tail length between treatment ways and time（ P〈0. 05）. The positive rate in light box defecation test of PG was higher than that of CG and HG（ P〈0. 05）,whereas the sucrose preference rate in PG was significantly lower than that of CG and HG（ P〈0. 05）. However,no statistically significant differences were observed between CG and HG（ P〈0. 05）. The serum level of dopamine in PG was lower than that in CG and HG（ P〈0. 05）,but no statistically significant differences were observed between CG and HG（ P〈0. 05）. Conclusion Jinkui Shenqi pills could alleviate growth retardation,abnormal behavior,and serum dopamine level disturbance of the offspring caused by PTSD- induced fetal injury. The regulation of offspring neurobiology disorder can be achieved by supplying kidney essence, thereby warming and invigorating the kidney yang, filling the marrow, and nourishing the cerebral spirit.