万氏牛黄清心丸中各单味药对朱砂肾毒性的配伍减毒作用研究
发布时间：2018-08-22 09:24
【摘要】：目的明确万氏牛黄清心丸组方中各单味药对朱砂致大鼠肾毒性的减毒作用,为进一步研究万氏牛黄清心丸对朱砂肾毒性配伍减毒作用的物质基础提供参考依据。方法实验选用健康SD大鼠(180±20g),雌雄各半,随机分为7组,每组24只,共168只。以朱砂+各单味药(朱砂+黄连、朱砂+黄芩、朱砂+栀子、朱砂+郁金、朱砂+牛黄)对大鼠灌胃,同时设立朱砂组、全方组,所有组含朱砂1.0g/kg,每天一次,连续给药12周。灌胃期间,观察大鼠的行为活动、外观体征、体重变化、饮食、分泌物、排泄物等,每周称体重2次,根据体重调整给药剂量。分别于给药4周、8周、12周和停药4周后收集24h尿液。取材前一晚,禁食不禁水,每组取6只大鼠,雌雄各半,充分麻醉后,取血液和肾脏。采用赛曼原子吸收汞分析仪测定血液、肾组织、尿液中的汞含量;全自动生化分析仪测定血清尿酸(Blood Uric Acid,BUA)和血清肌酐(Serum Creatinine,SCr)肾功相关指标;采用样本碱水解法测试盒检测肾组织羟脯氨酸含量;制作肾组织病理切片,HE(Hematoxylin-Eosin staining)染色和Masson染色,光镜下观察肾组织的病理改变;用Real-time PCR检测TNF-α(Tumor Necrosis Factor alpha)、IL-10(Interleukin-10)表达水平。数据以x±s表示,SPSS17.0统计软件分析,多组间比较采用单因素方差分析(One-Way ANOVA);组间两两比较,方差齐时用S-N-K法分析,方差不齐时用Dunnett’s T3法分析,检验水准α=0.05。结果实验期间所有动物一般状况良好,体重均正常增长,不同处理组间无显著性差异。给药4周、8周、12周、停药4周,血汞含量,朱砂与黄连、栀子、黄芩或郁金伍用,均低于单独使用朱砂组(P0.05),各配伍组均高于全方组(P0.05);给药4周、8周、12周、停药4周,肾汞含量,朱砂与黄莲、栀子或郁金伍用,均低于单独使用朱砂组(P0.05),各配伍组均高于全方组;给药4周、8周、12周、停药4周,尿汞含量,朱砂与黄莲或郁金伍用,均低于单独使用朱砂组(P0.05),朱砂与黄芩、栀子、郁金或牛黄伍用,高于全方组。给药8周、12周、停药4周,BUA含量,朱砂与黄芩、栀子、郁金或牛黄伍用,低于朱砂组(P0.05);给药8周、12周、停药4周,SCr含量,朱砂与黄连、黄芩、栀子、郁金或牛黄伍用,低于朱砂组(P0.05)。全方和朱砂与栀子伍用,大鼠肾脏呈暗红色(中草药色素),随着给药时间延长,颜色越深,停药4周后,有轻微好转;光镜下可见,单独使用朱砂组,肾小管上皮细胞空泡变性、肿胀、管腔狭小,部分肾小管结构消失,小管间隙增宽,管腔内可见蛋白管型,局部上皮细胞坏死,间质炎性细胞浸润(以淋巴细胞和单核细胞为主),间质轻度纤维增生,病变部位主要在肾皮髓交界处;全方组以及朱砂与各单方伍用,病变较单独使用朱砂组轻;全方和朱砂与栀子伍用可见色素沉积。给药12周,全方组大鼠肾组织TNF-α、IL-10相对表达量小于单用朱砂组(P0.05)。结论万氏牛黄清心丸全方对朱砂致大鼠肾毒性具有减毒作用;黄连、栀子、郁金与朱砂伍用,可减少汞吸收或促进尿汞排出,进而降低肾汞蓄积水平;万氏牛黄清心丸全方组及各单味药与朱砂配伍组肾损伤均比朱砂组轻;万氏牛黄清心丸全方比单味药与朱砂伍用拮抗朱砂肾毒性的效果更明显。
[Abstract]:Objective To clarify the detoxification effect of each single drug in Wanshi Niuhuang Qingxin pill group on cinnabar-induced nephrotoxicity in rats, and to provide reference for further study on the material basis of Wanshi Niuhuang Qingxin Pill on cinnabar-induced nephrotoxicity. Rats were fed with cinnabar + each single herb (cinnabar + Coptis chinensis, cinnabar + baicalein, cinnabar + gardenia, cinnabar + tulip, cinnabar + bovine bezoar) for 12 weeks. At the same time, rats were given cinnabar group, whole prescription group. All groups contained cinnabar 1.0 g/kg, once a day for 12 weeks. The urine samples were collected at 4, 8, 12 and 4 weeks after the drug was withdrawn. Serum uric acid (BUA) and serum creatinine (SCr) were measured by automatic biochemical analyzer; hydroxyproline content in renal tissue was detected by sample alkaline hydrolysis test kit; pathological sections of renal tissue were made, stained by HE (hematoxylin-Eosin staining) and Mason (Mason) and pathological changes of renal tissue were observed under light microscope. TNF-alpha (Tumor Necrosis Factor alpha) and IL-10 (Interleukin-10) levels were detected by Real-time PCR. Data were expressed by x+s and analyzed by SPSS17.0 statistical software. One-way ANOVA was used for multigroup comparisons; S-N-K was used for pairwise comparisons, and Dunnett's T3 was used for variance analysis when variance was uneven. Results During the experiment, all the animals were in good general condition, their weight increased normally, and there was no significant difference among different treatment groups. The content of mercury in kidney, the combination of cinnabar with huanglian, Gardenia or tulip was lower than that of cinnabar alone (P 0.05), and the content of mercury in urine was lower than that of cinnabar with huanglian, gardenia, tulip or bovis alone (P 0.05). The content of BUA was lower in cinnabar group than in cinnabar group (P With the prolongation of administration time, the darker the color, after 4 weeks of withdrawal, slightly improved; light microscopy showed that in the cinnabar group alone, renal tubular epithelial cells vacuole degeneration, swelling, narrow lumen, part of the renal tubular structure disappeared, tubular space widened, lumen visible protein tube type, local epithelial cell necrosis, interstitial inflammatory cell infiltration ( Lymphocyte and monocyte were the main cells, interstitial fibrosis was mild, and the lesion was mainly at the junction of renal cortex and medulla; the lesion was lighter in the whole prescription group and cinnabar combined with each other than that in the cinnabar alone group; pigment deposition was observed in the whole prescription and cinnabar combined with gardenia jasminoides. Conclusion The whole prescription of Wanshi Niuhuang Qingxin Pill can reduce the renal toxicity induced by cinnabar in rats, and the combination of Coptis chinensis, Gardenia jasminoides, Tulip and cinnabar can reduce the absorption of mercury in urine or promote the excretion of mercury in urine, thereby reducing the level of renal mercury accumulation. Wan's Niuhuang Qingxin pill is more effective than mono medicine and cinnabar in antagonizing cinnabar kidney toxicity.
【学位授予单位】：锦州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.1
[Abstract]:Objective To clarify the detoxification effect of each single drug in Wanshi Niuhuang Qingxin pill group on cinnabar-induced nephrotoxicity in rats, and to provide reference for further study on the material basis of Wanshi Niuhuang Qingxin Pill on cinnabar-induced nephrotoxicity. Rats were fed with cinnabar + each single herb (cinnabar + Coptis chinensis, cinnabar + baicalein, cinnabar + gardenia, cinnabar + tulip, cinnabar + bovine bezoar) for 12 weeks. At the same time, rats were given cinnabar group, whole prescription group. All groups contained cinnabar 1.0 g/kg, once a day for 12 weeks. The urine samples were collected at 4, 8, 12 and 4 weeks after the drug was withdrawn. Serum uric acid (BUA) and serum creatinine (SCr) were measured by automatic biochemical analyzer; hydroxyproline content in renal tissue was detected by sample alkaline hydrolysis test kit; pathological sections of renal tissue were made, stained by HE (hematoxylin-Eosin staining) and Mason (Mason) and pathological changes of renal tissue were observed under light microscope. TNF-alpha (Tumor Necrosis Factor alpha) and IL-10 (Interleukin-10) levels were detected by Real-time PCR. Data were expressed by x+s and analyzed by SPSS17.0 statistical software. One-way ANOVA was used for multigroup comparisons; S-N-K was used for pairwise comparisons, and Dunnett's T3 was used for variance analysis when variance was uneven. Results During the experiment, all the animals were in good general condition, their weight increased normally, and there was no significant difference among different treatment groups. The content of mercury in kidney, the combination of cinnabar with huanglian, Gardenia or tulip was lower than that of cinnabar alone (P 0.05), and the content of mercury in urine was lower than that of cinnabar with huanglian, gardenia, tulip or bovis alone (P 0.05). The content of BUA was lower in cinnabar group than in cinnabar group (P With the prolongation of administration time, the darker the color, after 4 weeks of withdrawal, slightly improved; light microscopy showed that in the cinnabar group alone, renal tubular epithelial cells vacuole degeneration, swelling, narrow lumen, part of the renal tubular structure disappeared, tubular space widened, lumen visible protein tube type, local epithelial cell necrosis, interstitial inflammatory cell infiltration ( Lymphocyte and monocyte were the main cells, interstitial fibrosis was mild, and the lesion was mainly at the junction of renal cortex and medulla; the lesion was lighter in the whole prescription group and cinnabar combined with each other than that in the cinnabar alone group; pigment deposition was observed in the whole prescription and cinnabar combined with gardenia jasminoides. Conclusion The whole prescription of Wanshi Niuhuang Qingxin Pill can reduce the renal toxicity induced by cinnabar in rats, and the combination of Coptis chinensis, Gardenia jasminoides, Tulip and cinnabar can reduce the absorption of mercury in urine or promote the excretion of mercury in urine, thereby reducing the level of renal mercury accumulation. Wan's Niuhuang Qingxin pill is more effective than mono medicine and cinnabar in antagonizing cinnabar kidney toxicity.
【学位授予单位】：锦州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.1
【相似文献】
相关期刊论文 前10条
1 张梅,夏厚林,万丽,何正有,魏阳,代琪;万氏牛黄清心丸中汞的不同存在状态与药效的关系[J];成都中医药大学学报;2001年04期
2 耿建军;关于《中国药典》万氏牛黄清心丸朱砂含量测定的商榷[J];中成药;2004年12期
3 傅大知，傅金汉;万氏牛黄清心丸的临床应用[J];浙江中医杂志;1995年09期
4 陈斌;李飞艳;李福元;;万氏牛黄清心丸中酸枣仁替代朱砂和去朱砂的实验研究之一——抗炎作用比较研究[J];中南药学;2011年03期
5 陈斌;李飞艳;李福元;;含与不含朱砂的万氏牛黄清心丸解热作用的实验研究[J];世界中西医结合杂志;2012年01期
6 李同芬;;比色-导数光谱法测定万氏牛黄清心丸中胆酸的含量[J];中成药;1989年09期
7 于立佐;;万氏牛黄清心丸中胆酸的薄层鉴别[J];中成药;1990年03期
8 陈伯o，
本文编号：2196681
本文链接：https://www.wllwen.com/yixuelunwen/mazuiyixuelunwen/2196681.html
最近更新
教材专著
