【摘要】：目的明確萬(wàn)氏牛黃清心丸組方中各單味藥對(duì)朱砂致大鼠腎毒性的減毒作用,為進(jìn)一步研究萬(wàn)氏牛黃清心丸對(duì)朱砂腎毒性配伍減毒作用的物質(zhì)基礎(chǔ)提供參考依據(jù)。方法實(shí)驗(yàn)選用健康SD大鼠(180±20g),雌雄各半,隨機(jī)分為7組,每組24只,共168只。以朱砂+各單味藥(朱砂+黃連、朱砂+黃芩、朱砂+梔子、朱砂+郁金、朱砂+牛黃)對(duì)大鼠灌胃,同時(shí)設(shè)立朱砂組、全方組,所有組含朱砂1.0g/kg,每天一次,連續(xù)給藥12周。灌胃期間,觀察大鼠的行為活動(dòng)、外觀體征、體重變化、飲食、分泌物、排泄物等,每周稱(chēng)體重2次,根據(jù)體重調(diào)整給藥劑量。分別于給藥4周、8周、12周和停藥4周后收集24h尿液。取材前一晚,禁食不禁水,每組取6只大鼠,雌雄各半,充分麻醉后,取血液和腎臟。采用賽曼原子吸收汞分析儀測(cè)定血液、腎組織、尿液中的汞含量;全自動(dòng)生化分析儀測(cè)定血清尿酸(Blood Uric Acid,BUA)和血清肌酐(Serum Creatinine,SCr)腎功相關(guān)指標(biāo);采用樣本堿水解法測(cè)試盒檢測(cè)腎組織羥脯氨酸含量;制作腎組織病理切片,HE(Hematoxylin-Eosin staining)染色和Masson染色,光鏡下觀察腎組織的病理改變;用Real-time PCR檢測(cè)TNF-α(Tumor Necrosis Factor alpha)、IL-10(Interleukin-10)表達(dá)水平。數(shù)據(jù)以x±s表示,SPSS17.0統(tǒng)計(jì)軟件分析,多組間比較采用單因素方差分析(One-Way ANOVA);組間兩兩比較,方差齊時(shí)用S-N-K法分析,方差不齊時(shí)用Dunnett’s T3法分析,檢驗(yàn)水準(zhǔn)α=0.05。結(jié)果實(shí)驗(yàn)期間所有動(dòng)物一般狀況良好,體重均正常增長(zhǎng),不同處理組間無(wú)顯著性差異。給藥4周、8周、12周、停藥4周,血汞含量,朱砂與黃連、梔子、黃芩或郁金伍用,均低于單獨(dú)使用朱砂組(P0.05),各配伍組均高于全方組(P0.05);給藥4周、8周、12周、停藥4周,腎汞含量,朱砂與黃蓮、梔子或郁金伍用,均低于單獨(dú)使用朱砂組(P0.05),各配伍組均高于全方組;給藥4周、8周、12周、停藥4周,尿汞含量,朱砂與黃蓮或郁金伍用,均低于單獨(dú)使用朱砂組(P0.05),朱砂與黃芩、梔子、郁金或牛黃伍用,高于全方組。給藥8周、12周、停藥4周,BUA含量,朱砂與黃芩、梔子、郁金或牛黃伍用,低于朱砂組(P0.05);給藥8周、12周、停藥4周,SCr含量,朱砂與黃連、黃芩、梔子、郁金或牛黃伍用,低于朱砂組(P0.05)。全方和朱砂與梔子伍用,大鼠腎臟呈暗紅色(中草藥色素),隨著給藥時(shí)間延長(zhǎng),顏色越深,停藥4周后,有輕微好轉(zhuǎn);光鏡下可見(jiàn),單獨(dú)使用朱砂組,腎小管上皮細(xì)胞空泡變性、腫脹、管腔狹小,部分腎小管結(jié)構(gòu)消失,小管間隙增寬,管腔內(nèi)可見(jiàn)蛋白管型,局部上皮細(xì)胞壞死,間質(zhì)炎性細(xì)胞浸潤(rùn)(以淋巴細(xì)胞和單核細(xì)胞為主),間質(zhì)輕度纖維增生,病變部位主要在腎皮髓交界處;全方組以及朱砂與各單方伍用,病變較單獨(dú)使用朱砂組輕;全方和朱砂與梔子伍用可見(jiàn)色素沉積。給藥12周,全方組大鼠腎組織TNF-α、IL-10相對(duì)表達(dá)量小于單用朱砂組(P0.05)。結(jié)論萬(wàn)氏牛黃清心丸全方對(duì)朱砂致大鼠腎毒性具有減毒作用;黃連、梔子、郁金與朱砂伍用,可減少汞吸收或促進(jìn)尿汞排出,進(jìn)而降低腎汞蓄積水平;萬(wàn)氏牛黃清心丸全方組及各單味藥與朱砂配伍組腎損傷均比朱砂組輕;萬(wàn)氏牛黃清心丸全方比單味藥與朱砂伍用拮抗朱砂腎毒性的效果更明顯。
[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 The urine samples were collected at 4, 8, 12 and 4 weeks after the drug was withdrawn.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.
【學(xué)位授予單位】：錦州醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R285.1

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