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基于快速型心律失常大鼠模型优选白喉乌头炮制品

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目的 优选可预防模型大鼠快速型心律失常的白喉乌头炮制品。方法 采用哈萨克族炮制法,分别浸泡白喉乌头生品 12h和24 h,加甘草和黑豆共同煎煮 1,2,3,4 h,得 8 种炮制品。将 96 只大鼠随机分为空白对照组(等体积生理盐水),模型组(等体积生理盐水),白喉乌头生品药物组(简称生药组,0。4 g/kg),白喉乌头炮制品8个组(1。2g/kg,分别记为12h-1h组、12h-2h组、12h-3h组、12h-4h组、24h-1h组、24h-2h组、24h-3h组、24h-4h组),胺碘酮组(5 mg/kg),各 8 只。各组大鼠每天 1 次灌胃相应药物或生理盐水,连续 14d后空白对照组大鼠尾静脉注射等体积生理盐水,其余各组大鼠均注射 10 mg/mL乌头碱(3。125 mg/kg)以复制快速型心律失常模型。检测大鼠的心电图,显微镜下观察大鼠的心脏组织病理形态,采用酶联免疫吸附法检测超氧化物歧化酶(SOD)、丙二醛(MDA)、肌酸激酶同工酶MB(CK-MB)、心肌肌钙蛋白I(cTnI)水平,检测心肌三磷酸腺苷(ATP)酶活性,采用免疫组化染色法检测心脏组织Cx45 蛋白表达水平。结果 24h-1h组大鼠未出现心室颤动(室颤)、室性心动过速(室速)、期前收缩(早搏)症状,其余炮制品 7 个组及胺碘酮组大鼠均出现早搏及室速的时间均晚于模型组。模型组大鼠心肌纤维排列紊乱,心肌纤维断裂较多;炮制品 8 个组及胺碘酮组大鼠心肌纤维排列均较规则,心肌纤维断裂较少,心肌细胞水肿损伤程度降低。与模型组比较,炮制品 8个组大鼠心肌组织的SOD,Cx45 蛋白表达水平,以及 24h-2h组、24h-3h组Ca2+-ATP酶水平均显著升高(P<0。05);生药组、12h-1h组、12h-2h组、24h-1h组大鼠血清MDA水平均显著降低(P<0。05);各给药组(除 24h-2h组、24h-3h组外)大鼠血清cTnI水平均显著降低(P<0。05);各给药组(除 24h-3h组外)大鼠血清CK-MB水平均显著降低(P<0。05)。结论 哈萨克族炮制法制成的白喉乌头炮制品对模型大鼠快速型心律失常均有一定预防作用,其中以 24h-1h炮制品效果较显著。
Optimization of Processed Aconitum Leucostomum Based on Rat Models of Rapid Arrhythmia
Objective To optimize the processed Aconitum leucostomum that can prevent rapid arrhythmia in model rats.Methods The Kazak processing method was adopted.The raw Aconitum leucostomum was soaked for 12 h and 24 h respectively,and then boiled together with Glycyrrhizae Radix et Rhizoma and Sojae Semen Nigrum for 1,2,3,4 h to obtain eight processed products.A total of 96 rats were randomly divided into the blank control group(equal volume of physiological saline),the model group(equal volume of physiological saline),the raw Aconitum leucostomum group(referred to as the raw drug group,0.4 g/kg),the eight processed Aconitum leucostomum groups(1.2 g/kg,recorded as 12 h-1 h group,12 h-2 h group,12 h-3 h group,12 h-4 h group,24 h-1 h group,24 h-2 h group,24 h-3 h group,24 h-4 h group respectively),the amiodarone group(5 mg/kg),with eight rats in each group.The rats in each group were given corresponding drugs or physiological saline by gavage once a day for 14 d;after that,the blank control group was injected with an equal volume of physiological saline via the tail vein,while the other groups were injected with 10 mg/mL aconitine(3.125 mg/kg)to replicate the rapid arrhythmia models.The electrocardiogram of rats was detected,the pathological morphology of cardiac tissue in rats was observed by microscope,the superoxide dismutase(SOD),malondialdehyde(MDA),creatine kinase isoenzyme MB(CK-MB),cardiac troponin I(cTnI)levels were detected by the enzyme-linked immunosorbent assay,the activity of myocardial adenosine triphosphatase(ATPase)was detected,and the expression level of Cx45 protein in cardiac tissue was detected by the immunohistochemistry staining method.Results No ventricular fibrillation,ventricular tachycardia or premature beat was observed in the 24 h-1 h group,the premature beats and ventricular tachycardia in the other seven processed product groups and the amiodarone group occurred later than those in the model group.The myocardial fibers had disordered arrangement and obvious rupture in the model group;while those were better in the eight processed product groups and amiodarone group,and the edema and damage of myocardial cells relieved.Compared with those in the model group,the expression levels of SOD and Cx45 proteins of myocardial tissues in the eight processed product groups and the Ca2 +-ATPase level in the 24 h-2 h group and 24 h-3 h group were significantly higher(P<0.05);the serum MDA level in the raw drug group,12 h-1 h group,12 h-2 h group and 24 h-1 h group was significantly lower(P<0.05);the serum cTnI level in all the drug groups(except for the 24 h-2 h group and 24 h-3 h group)was significantly lower(P<0.05);and the serum CK-MB level in all the drug groups(except for the 24 h-3 h group)was significantly lower(P<0.05).Conclusion The processed Aconitum leucostomum by Kazak processing method have a certain preventive effect on the rapid arrhythmia in model rats,among which the 24 h-1 h processed product is more effective.

Aconitum leucostomumKazak processing methodrapid arrhythmiarat

崔梦茹、赵翡翠、聂继红、张海英、赵生俊

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新疆医科大学第四临床医学院,新疆 乌鲁木齐 830000

新疆医科大学附属中医医院,新疆 乌鲁木齐 830000

新疆中药炮制研究重点实验室,新疆 乌鲁木齐 830000

白喉乌头 哈萨克族炮制法 快速型心律失常 大鼠

国家自然科学基金

81160498

2024

中国药业
重庆市食品药品监督管理局

中国药业

CSTPCD
影响因子:1.369
ISSN:1006-4931
年,卷(期):2024.33(6)
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