ABSTRACT
Disorders of the gut flora (GF) affect the level of 5-hydroxytryptamine (5-HT) in the brain of patients with generalized anxiety disorder (GAD) and influence the development of the disease. Most of the acupuncture points selected for GAD are based on the principles of local acupuncture points and acupuncture points following the distant channels of the meridians, regarding Baihui (DU 20), Fengchi (GB 20), and Yintang (GV 29) as the main acupuncture points, and the acupuncture points selected for the regulation of GF are Zhongwan (CV 12), Tianshu (ST 25), and Guanyuan (RN 4) and Zusanli (ST 36). Recently, many studies have been conducted on the mechanism of action of acupuncture in the treatment of GAD from the perspective of GF, but few have investigated the theoretical of acupuncture points used to prevent and treat GAD. This paper discusses the theoretical basis of acupuncture to regulate the "microbiota-gut-brain axis" (MGBA) for the prevention and treatment of GAD, and proposes the method of "regulating the internal organs and calming the mind and relieving anxiety" through analyzing the researches on the regulation of GF and GAD.
ABSTRACT
OBJECTIVE To explore potential proarrhythmic effect and underlying mechanism of azithromycin (AZM) and Shengmai injection (SM) used clinically.METHODS ① In vivo guinea pig ECG recordings were made to analyze effects of jugular intravenous(iv) injection of AZM [38.2 mg· kg-1,one time (clinically relevant dose,CRD)],or SM (4.6 mL· kg-1,one time CRD) or their combination.②In vitro ECG recordings were made to analyze effects of AZM,SM or AZM + SM on ECG in isolated hearts of guinea pigs.AZM [one,five and ten times (clinically relevant concentrations,CRC)] was perfused in this order:41.5 →207.5 → 415 mg· L-1 and SM (one,five and ten times CRC) in this order:5 →25 →50 mL· L-1.Also,AZM (41.5 mg· L-1,one time CRC) +SM (5 mL· L-1,one time CRC) was perfused to isolated hearts of guinea pigs.③ Enzymatically isolated cardiomyocytes from guinea pig left ventricles were perfused in this order:AZM 41.5 mg· L-1 →AZM 41.5 mg· L-1+SM 5 mL· L-1 for action potential,L-type Ca2+ and Na+ current recordings,respectively.RESULTS ① Neither AZM 38.2 mg· kg-1,nor SM 4.6 mL· kg-1 significantly changed the in vivo ECG.However,AZM 38.2 mg· kg-1 +SM 4.6 mL · kg-1 significantly reduced heart rate (P＜0.05) and prolonged the P-R (P＜0.05) and QRS (P＜0.05) intervals.②AZM 41.5,207.5 and 415 mg· L-1 reduced heart rate (P＜0.05) and prolonged the P-R (P＜0.05) and QRS (P＜0.05) intervals in a concentration-dependent manner.AZM 415 mg·L-1 also prolonged QTc (P＜0.05) interval.SM 5,25 and 50 mL· L-1 reduced heart rate (P＜0.05) and prolonged the P-R interval (P＜0.05) in a concentration-dependent manner.SM had no effect on QRS or QTc intervals.Washout partially recovered the above changes.Moreover,AZM 41.5 mg· L-1 + SM 5 mg·L-1 significantly reduced heart rate (P＜0.05) and prolonged the P-R (P＜0.05) and QRS intervals.③ AZM 41.5 mg·L-1 did not significantly change the action potential amplitude (APA),action potential durations at 50％ (APD50) and 90％ (APD90) repolarization levels,or L-type Ca2+ and Na+ currents.However,AZM+SM 5 mg· L-1 significantly reduced APA (P＜0.05),shortened APD50 (P＜0.05) and APD90 (P＜0.05) and inhibited the L-type Ca2+ (P＜0.05) and Na+ (P＜0.05) currents.CONCLUSION AZM and SM has potential prorrhythmic risks.The combined use might cause higher risk of arrhythmia.The underlying mechanism for proarrhythmia is mediated by inhibition of the L-type Ca2+ and Na+ currents.
ABSTRACT
OBJECTIVE To explore kinetic features and its underlying mechanism of the positive inotropic effect of liguzinediol(LZDO)in rats. METHODS ①An In vivo study was made to record the effect of LZDO 20 mg · kg-1 injected for 30 consecutive min from the left external jugular vein on pressure-volume relationships. ②Ex vivo study was used to record the antagonistic effect of LZDO on reduced contractility induced by caffeine. Caffeine and LZDO were perfused as follows:normal perfusion solution, caffeine 0.5 mmol · L-1,and then caffeine 0.5 mmol · L-1+LZDO 100 μmol · L-1. ③ Ca2+ transient from cardiomyocyte sarcoplasmic reticulum (SR) was measured to analyze the effect of LZDO on Ca2 +release blocked by thapsigargin. Thapsigargin and LZDO were perfused as follows:normal perfusion solution,thapsigargin 2 μmol · L-1,and then thapsigargin 2 μmol · L-1+LZDO 100 μmol · L-1.④The SR vesicles were prepared and the effect of LZDO(1,10 and 100μmol·L-1)on sarcoplasmic reticulum Ca2+ATPase(SERCA2a)activity was determined according to the ultramicro-Ca2+-ATP enzyme kit. RESULTS ① LZDO 20 mg · kg- 1 significantly reduced the end-systolic volume (Ves) and enhanced the end-systolic pressure (Pes),stroke volume (SV),ejection fraction (EF),cardiac output(CO),peak rate of rise of left ventricular pressure(+dp/dtmax)and stroke work(SW)(P<0.05). However,LZDO 20 mg · kg-1 did not significantly change the heart rate(HR )or the end-diastolic volume (Ved). ② Caffeine 0.5 mmol · L- 1 significantly enhanced HR,left ventricular developed pressure (LVDP ),and+dp∶dtmax at 5 min after caffeine and decreased at 30 min. However,LZDO 100μmol·L-1 restored the reduced HR,LVDP,and+dp/dtmax induced by caffeine at 30 min(P<0.05).③Thapsigargin 2μmol·L-1 significantly reduced the SR Ca2+transient from perfusion solution group(100±5)%to(51± 5)%(P<0.05) and LZDO 100 μmol · L-1 failed to restore the decreased Ca2+ transient〔(49 ± 4)%〕. Normalized Ca2+transients were reduced by thapsigargin 2μmol·L-1 and thapsigargin 2μmol·L-1+LZDO 100 μmol · L-1. ④ LZDO(10 and 100 μmol · L-1)significantly increased the activities of SERCA2a in perfusion solution group 0.98±0.10 to 1.17±0.20 and (1.43±0.09)μmol Pi·g-1·h-1,respectively(P<0.05). CONCLUSION LZDO can enhance SR Ca2+ gradient by activating the SERCA2a and might be developed to serve as a potential positive inotropic agent in clinical settings.