1.Study on the Toxicity Mechanism of Yunaconitine-induced Arrhythmia in Rats Based on Calcium Overload
Zhisi ZHANG ; Wanqiu CHENG ; Tao JIANG ; Zhibin SHEN ; Yanfen CHEN ; Cong CHEN ; Ying SITU ; Chunping TANG
China Pharmacy 2021;32(23):2854-2858
OBJECTIVE:To study the toxicity mechanism of yunacotine-induced arrhythmia in rats. METHODS :Totally 32 rats were randomly divided by random number table method into normal control group ,yunacotine low-dose and high-dose groups (0.09,0.14 mg/kg),aconitine group (positive control ,0.88 mg/kg),with 8 rats in each group. Administration groups were given the corresponding drugs once a day ,and normal control group was given the constant volume of normal saline ,for consecutive 7 d. After last intragastric administration ,the changes of electrocardiogram (ECG) were observed. The contents of adenosine triphosphate(ATP)in myocardial tissue and Ca 2+ in myocardial cells ,the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase as well as the protein expression of ranolidine receptor 2(RyR2)and Ca 2+-ATPase(SERCA2)in myocardial tissue were determined. RESULTS:Compared with normal control group ,time limit of QRS wave and QTc intervals of rats were prolonged significantly in yunaconitine low-dose group (P<0.01). The content of Ca 2 + in myocardial cells , the ATP contents , the activities of Ca2+-Mg2+-ATPase and Na +-K+-ATPase as well as the protein expression of SERCA 2 in myocardial tissue were reduced significantly (P<0.05 or P<0.01). The heart rate of rats in yunaconitine high-dose group and aconitine group were increased significantly (P< 0.05 or P<0.01),and time limit of QRS wave and QTc intervals were significantly prolonged (P<0.01);the content of Ca 2+ in myocardial cells was increased significantly (P<0.01);ATP content ,the activities of Ca 2+-Mg2+-ATPase and Na +-K+-ATPase,and protein expression of RyR 2 and SERCA 2 in myocardial tissue were decreased significantly (P<0.01). CONCLUSIONS : Yunaconitine can induce arrhythmia in rats ,the mechanism of which may be associated with Ca 2+ overload that resulted from reducing the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase and down-regulating the expression of related calcium transporter RyR2 and SERCA 2.
2.Study on Effects and Active Ingredients of Tibetan Medicine Lamiophlomis rotata against Rheumatoid Arthritis ZHANG Yanfei ,CHEN Ruixin ,YUAN Maohua ,YANG Zhizhong ,HUANG Ting ,CHEN Suxian ,JIANG Yunbin (578) Effects of Isoflavaspidic Acid PB on the Biofilm Adhesion and Gene Expression of Ergosterol Metabolism Related Enzymes in Trichophyton rubrum
Jie HOU ; Chunping TANG ; Zhibin SHEN ; Yanfen CHEN ; Shen DING ; Zhisi ZHANG ; Xiaoying LI ; Tao JIANG
China Pharmacy 2021;32(5):584-589
OBJECTIVE:To study the effect of isofla vaspidicacid PB (called PB for short )on the biofilm adhesion and the gene expression of ergosterol metabolism related enzymes in Trichophyton rubrum . METHODS :M38-A2 method was adopted to determine MIC of PB to T. rubrum . MTT assay was used to screen the biolfilm condition and initial adhesion period of T. rubrum . The effects of different concentrations of PB (40,80,160 µg/mL)on the adhesion duration of T. rubrum (growth control group without PB was set up ,similarly hereinafter )were evaluated and the adhesion rate was calculated by using XTT assay ;the effects of different concentrations of PB (20,40,80 µg/mL)on the biofilm formation of T. rubrum at different initial adhesion periods (3,5,9 h)were observed and the adhesion rate was calculated by using XTT assay combined with inverted microscope ;qRT-PCR method was used to detect the effects of PB (320 µg/mL)on the mRNA expression of ergosterol metabolism related enzyme gene ERG6 and ERG11 in biofilm of T. rubrum . RESULTS :MIC of PB to T. rubrum was 20 µg/mL. The biofilm of T. rubrum in RPMI-1640 medium containing 10% FBS was the most metabolism activity at 6 h of initial adhesion. Compared with growth control group ,after treated with different concentrations of PB ,adhesion rate and mRNA expression of ERG6 and ERG11 in biofilm were decreased significantly (P<0.01). Hyphae decreased or even disappeared ,and the adhesion inhibition rate (at 5 and 9 h of initial adhesion )increased significantly (P<0.05 or P<0.01). CONCLUSIONS :PB can inhibit the adhesion of T. rubrum and reduce the hyphae ;the mechanism may be associated with the inhibition of the biofilm adhesion and mRNA expression of ergosterol metabolism related enzyme gene ERG6 and ERG11.