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天南星和虎掌南星胆汁炮制前后毒性对比研究

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目的:探讨胆汁制天南星和虎掌南星前后的急性毒性、刺激性和燥性效应变化。方法:将132只小鼠随机分组后进行急性毒性试验;39只家兔随机分组后进行兔眼刺激试验;104只大鼠随机分组进行燥性试验。以小鼠中毒表现、兔眼刺激评分和大鼠的饮水量、排尿指数、大便含水率和颌下腺、肾脏、结肠的病理变化以及水通道蛋白5(Aquaporin5,AQP5)、AQP2、AQP3的表达、血浆粘度、血清中环磷腺苷/环磷酸鸟苷(adenosine cyclic 3',5'-hydrogen phosphate/current good manufacture practices,cAMP/cGMP)、三磷酸腺苷酶(ATPase,Na+-K+-ATP酶)、血浆中的肌酐(Cr)和尿素氮(BUN)含量等指标进行考察。结果:天南星和虎掌南星胆汁炮制前后的水煎液对小鼠灌胃无毒性,小鼠最大耐受量生品均为108 g/kg,炮制品均为75。6 g/kg。胆汁炮制后对家兔眼刺激的作用显著减弱(P<0。05);天南星和虎掌南星对正常大鼠结肠、颌下腺、肾脏有明显损伤作用;显著升高血浆中Cr和BUN的含量(P<0。05或P<0。01),胆汁炮制后对正常大鼠结肠、颌下腺、肾脏组织损伤作用较弱。天南星和虎掌南星可使正常大鼠血液中cAMP/cGMP、Na+-K+-ATP酶含量和肾脏、结肠、颌下腺组织中水通道蛋白(AQP2、AQP3、AQP5)表达异常(P<0。05或P<0。01),使正常大鼠出现水液代谢紊乱、血液黏度增加、排尿指数增加、排便量减少、大便干结(P<0。05或P<0。01),各胆汁制南星组大鼠相应的指标考察中发现与生品相比其作用较弱。结论:胆汁炮制可使天南星和虎掌南星刺激性和燥性减弱,本研究可为天南星的"炮制缓燥"和"炮制减毒"提供科学依据。
Comparative Study on Toxicity of ARISAEMATIS RHIZOMA and Pinelliae Pedatisectae Schott Before and After Processing with Bile
Objective:To investigate the changes of acute toxicity,irritation,and dryness of ARISAEMATIS RHIZOMA and Pinelliae Pedatisectae Schott before and after processing with bile.Methods:A total of 132 mice were randomly divided,and an acute toxicity test was performed.39 rabbits were randomly divided,and an eye stimulation test was carried out.A total of 104 rats were randomly divided to perform a dryness test.The toxic manifestation of rats in each group,irritation score of rabbit eyes,water intake of rats,urination index,water content of stool,the pathological changes of submandibular gland,kidney,and colon,the expression levels of aquaporin 5(AQP5),aquaporin 2(AQP2),and aquaporin 3(AQP3),the plasma viscosity,and the contents of adenosine cyclic 3',5'-hydrogen phosphate/current good manufacture practices(cAMP/cGMP),ATPase(Na+-K+-ATPase),creatinine(Cr),and blood urea nitrogen(BUN)in plasma were determined.Results:The wa-ter decoction of ARISAEMATIS RHIZOMA and Pinelliae Pedatisectae Schott before and after processing with bile was non-toxic for rats.The maximum tolerance dose of ARISAEMATIS RHIZOMA and Pinelliae Pedatisectae Schott for rats was 108 g/kg,and that of ARISAEMATIS RHIZOMA and Pinelliae Pedatisectae Schott after processing with bile for rats was 75.6 g/kg.The stimulation on rabbit eyes of ARISAEMA-TIS RHIZOMA and Pinelliae Pedatisectae Schott after processing with bile significantly decreased(P<O.05).The damage effects of ARISAE-MATIS RHIZOMA and Pinelliae Pedatisectae Schott on the colon,submandibular gland,and kidney in normal mice were obvious.ARISAE-MATIS RHIZOMA and Pinelliae Pedatisectae Schott significantly increased the contents of Cr and BUN in plasma(P<0.05 or P<0.01).Af-ter processing with bile,their damage effects on the colon,submandibular gland,and kidney in normal mice were alleviated.In addition,ARISAEMATIS RHIZOMA and Pinelliae Pedatisectae Schott could make the content of cAMP/cGMP and ATPase in blood and the expression of aquaporins(AQP2,AQP3,and AQP5)in the kidney,colon,and submandibular gland of normal mice abnormal(P<0.05 or P<0.01).They could also cause disordered body fluid metabolism,increased blood viscosity,enhanced urination index,decreased defecation volume,and dry stool(P<0.05 or P<0.01)in normal mice.Compared with raw materials,it was found by analyzing the indexes of mice that the effect of ARISAEMATIS RHIZOMA and Pinelliae Pedatisectae Schott after processing with bile was weaker.Conclusion:Bile processing of ARISAEMATIS RHIZOMA and Pinelliae Pedatisectae Schott weakens their irritation and dryness,which can provide a scientific basis for dry-ness and toxicity reduction by processing of ARISAEMATIS RHIZOMA.

ARISAEMATIS RHIZOMAPinelliae Pedatisectae SchottBovine bileARISAEMA CUM BILEDrynessToxicity

武旭、钟恋、王晶、邹婷、杨凯、雷晗丹、党明、贺素容、张桥、卫培峰、赵重博

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陕西中医药大学陕西省中药饮片工程技术研究中心,咸阳 712046

陕西省中药炮制技术传承基地,咸阳 712046

四川省药品检验研究院,成都 611137

西安大兴医院,西安 710000

陕西中医药大学第二附属医院,咸阳 712046

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天南星 虎掌南星 牛胆汁 胆南星 燥性 毒性

国家自然科学基金青年基金中国药品监管科学行动计划重点项目(第二批)四川省药品检验研究院院立科研项目四川省自然科学基金陕西省中医药局"双链融合"中青年科研创新团队项目

81803732NMPAJGKX-2023-0772023-KYYL-0012022NSFSC15722022-SLRH-YQ-008

2024

中药药理与临床
中国药理学会 四川省中医药科学院

中药药理与临床

北大核心
影响因子:0.996
ISSN:1001-859X
年,卷(期):2024.40(3)
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