大黄蒽醌类成分肝肾毒性和效应物质研究  

Study on the liver and kidney toxicity and effective substances of rhubarb anthraquinone

作　　者：窦志华[1] 许波 施忠[1] 王陈萍[1] 宣东平[1] DOU Zhi- hua;XU Bo;SHI Zhong;WANG Chen -ping;XUAN Dong - ping(Department of Pharmacy, Nantong Third Affiliated Hospital of Nantong University, Nantong 226006, Jiangsu Province, China;Department of Pharmacy, Nantong Maternity and Child Health Hospital, Nantong 226019, Jiangsu Province, China)

机构地区：[1]南通大学附属南通第三医院药学部,江苏南通226006 [2]南通市妇幼保健院药学部,江苏南通226019

出　　处：《中国临床药理学杂志》2018年第10期1214-1217,共4页The Chinese Journal of Clinical Pharmacology

基　　金：江苏省"333工程"资助科研课题基金资助项目(BRA2013090);江苏省中医药局科技基金资助项目(LZ13168);江苏省南通市应用基础研究计划课题基金资助项目(MS12016057)

摘　　要：目的研究大黄蒽醌类成分的肝肾毒性和效应物质。方法大鼠灌胃大黄游离型蒽醌提取物制备含药血清。采用血清药理学方法,分别以谷草转氨酶(AST)和乳酸脱氢酶(LDH)泄漏量为指标,考察不同剂量含药血清对HL-7702和HK-2细胞的毒性。用血清药化学方法,测定含药血清的HPLC色谱图,并提取各色谱峰紫外吸收光谱图,与空白血清色谱图比较,指认含药血清中的药源性成分,与提取物及对照品色谱图和光谱图比对,分析药源性成分的来源并鉴定部分成分。结果与相应剂量空白血清细胞组比较,100%和80%含药血清组HL-7702细胞AST泄漏明显增加[(160.67±19.35)U·L^(-1)vs(113.33±2.08)U·L^(-1),(123.00±7.00)U·L^(-1)vs(82.33±11.93)U·L^(-1)],差异均有统计学意义(均P<0.01),100%,80%及40%含药血清组HK-2细胞LDH泄漏明显增加[(644.33±9.29)U·L^(-1)vs(606.67±11.85)U·L^(-1),(624.33±34.95)U·L^(-1)vs(504.33±16.04)U·L^(-1),(603.67±42.83)U·L^(-1)vs(398.00±19.08)U·L^(-1)],差异均有统计学意义(P<0.05或P<0.01)。大鼠灌胃大黄游离型蒽醌提取物后含药血清中产生了20个药源性成分,其中5个为原形游离型蒽醌,15个为代谢产物。5个为原形游离型蒽醌分别鉴别为芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚,15个为代谢产物中的8个分别鉴别为芦荟大黄素-8-O-葡萄糖苷、大黄酸-8-O-葡萄糖苷、大黄素-1-O-葡萄糖苷、大黄酚-1-O-葡萄糖苷、大黄酚-8-O-葡萄糖苷、大黄素-8-O-葡萄糖苷、芦荟大黄素-3-羟甲基-O-葡萄糖苷和大黄素甲醚-8-O-葡萄糖苷,其余7个代谢产物也具有蒽醌类成分的紫外吸收特征。结论大黄蒽醌类成分具有肝肾毒性,其效应物质为体内代谢产生的结合型蒽醌及体外原形游离型蒽醌。Objective To study the liver and kidney toxicity and effective substances of rhubarb anthraquinone. Methods Rat serums containing drugs(SCDs） were prepared after intragastric administration of the rhubarb extract of free anthraquinones. The toxicity of different doses of SCDs on HL-7702 and HK-2 cells were investigated using the method of serum pharmacology with aspartate aminotransferase(AST） and lactate dehydrogenase(LDH） leakage as the indexes. Using the serum pharmacochemistry method,the chromatogram of SCDs was detected by HPLC,and the UV absorption spectrograms of peaks were extracted. Comparing the chromatogram of SCDs with that of blank serum,drug-induced constituents in blood were analyzed. By comparing the chromatograms andspectrograms with those of extracts and reference substances,the sources of the drug-induced components were analyzed and some constituents were identified. Results Compared with the cells of corresponding blank serum groups,the leakage of AST in HL-7702 cells significantly increased in 100% and 80% SCDs groups [(160. 67 ± 19. 35）U·L-1 vs(113. 33 ± 2. 08） U·L-1,(123. 00 ± 7. 00） U·L-1 vs(82. 33 ± 11. 93） U·L-1],the differences were statistically significant(all P〈0. 01）,and the leakage LDH in HK-2 cells significantly increased in 100%,80% and40% SCDs groups [(644. 33 ± 9. 29） U · L-1 vs(606. 67 ± 11. 85） U · L-1,(624. 33 ± 34. 95） U · L-1 vs(504. 33 ± 16. 04） U·L-1,(603. 67 ± 42. 83） U·L-1 vs(398. 00 ± 19. 08） U·L-1],the differences were statistically significant(P〈0. 05 or P〈0. 01）. Twenty drug-induced components were detected in rat serum after intragastric administration of the rhubarb extract of free anthraquinones,five of them were the original free anthraquinones and fifteen were metabolites. Five original free anthraquinones were identified as aloe emodin,rhein,emodin,chrysophanol,and physcion. Eight constituents out of 15 metabolites were identified as aloe emodin-8-O-glucopyranoside,rhein-8-O-glucopyranoside,emodin-1-O-g

关 键 词：大黄 蒽醌 血清药理学 血清药化学 肝肾毒性 药效物质 

分 类 号：R28[医药卫生—中药学]