DHEA诱导雌性大鼠PCOS模型早期性器官及其相关激素变化的研究

本研究旨在探讨大鼠卵巢囊肿形成过程中,大鼠性腺等器官增重、性激素水平以及卵巢组织抗苗勒管激素AMH mRNA变化关系。选取性未成熟的雌性SD大鼠80只(21d),随机分为两组:试验组和对照组各40只。试验组大鼠颈部皮下注射0.2mL·d-1芝麻油+DHEA(每100g体重注射6mg DHEA);对照组注射等量注射用油,预试期2d,正试期20d。分别在试验开始第5、10、15和20天称取大鼠的体重、卵巢、子宫、肝、肾和脾的重量,计算脏器指数,采集血液备用。结果显示,第15和20天试验组大鼠的体重高于对照组(P0.01);试验组大鼠子宫重量显著高于对照组(P0.01),第5和10天卵巢重量显著高于对照组(P0.01);试验组血清AMH和雄激素(T)均显著高于对照组(P0.01或P0.05),第15和20天血清P以及第20天血清LH和E2试验组均显著高于对照组(P0.01或P0.05);试验组卵巢AMH mRNA表达量高于对照组,第5和10天表达量差异显著(P0.05)。结果提示,试验组大鼠性器官在性发育早期得到优先发育;抗苗勒管激素异常分泌可能是大鼠PCOS发病机理和发展的标志;卵巢AMH mRNA表达与血清AMH分泌变化规律并不完全一致,可能为深入研究多囊卵巢综合征的发生机制提供依据。     

玉米赤霉烯酮对雌性大鼠卵巢颗粒细胞凋亡相关蛋白Fas及FasL表达的影响

为了研究玉米赤霉烯酮(ZEA)对大鼠卵巢颗粒细胞Fas和FasL蛋白表达的影响。将36只8周龄雌性SD大鼠随机分为试验组和对照组,处理组腹腔注射5mg/kg ZEA玉米油溶液,对照组注射等剂量玉米油溶液。2组在注射后6、12、18、24、36、48h各处死3只,取出卵巢组织,4%多聚甲醛固定,免疫组化方法检测不同时间卵巢颗粒细胞Fas和FasL蛋白的表达情况。结果显示:试验组卵巢颗粒细胞Fas和FasL蛋白表达量均明显高于对照组(P<0.05),且随着时间的推进呈现动态变化。试验组Fas在各时间点表达量均显著高于对照组,且在18h时表达量最高,之后逐渐下降;试验组FasL表达量显著升高,在18和24h表达量显著上调。ZEA诱导大鼠卵巢颗粒细胞凋亡过程中,可能激活Fas和FasL相关的死亡受体信号通路。     

脱氢表雄酮对雄性衰老大鼠类固醇激素代谢的影响

以D-半乳糖诱导衰老大鼠为研究对象,探讨脱氢表雄酮(DHEA)对衰老大鼠部分类固醇激素代谢的影响。选用清洁级SD大鼠108只,随机分为4组,即阴性对照组、阳性对照组、DHEA低剂量组、DHEA高剂量。阴性对照组注射无菌生理盐水,其余每千克体重颈背部皮下注射150 mg/d的D-半乳糖溶液,共56 d。第57天,低剂量和高剂量组每千克体重分别一次性注射DHEA(溶解于50%无水乙醇和50%1.2-丙二醇中)25 mg、100 mg,其余各组注射等量的溶剂。分别在0,3,6,12和24 h宰杀大鼠,采样保存。结果表明:高剂量DHEA在24 h能显著降低大鼠血清总胆固醇(TC)含量(P<0.05)。注射低剂量DHEA后3 h显著降低高密度脂蛋白(HDL-C)含量(P<0.05),达到24 h又显著升高HDL-C的含量(P<0.05);而注射高剂量的DHEA则在3,6,24 h均显著降低HDL-C的含量(P<0.05)。高、低剂量的DHEA均在注射后3 h使大鼠血清T、雌二醇(E2)、孕酮(P)、皮质醇(Cor)含量达到最大值,而后随着时间的延长又逐渐降低。     

mC3d3-DINHα(1～32)基因免疫对大鼠卵泡发育和生殖激素的影响

选择32只60日龄雌性性成熟大鼠分为4组,分别肌肉注射pcDNA-DPPISS-DINH(试验组1) 50 μg,pcDNA-DPPISS-DINH-mC3d3 (试验组2) 50 μg,空载体pcDNA3.1 (对照组1) 50 μg,生理盐水(对照组2)1 mL.首次免疫20、40 d后各组分别同剂量同样免疫程序加强免疫注射1次.结果发现,试验1和2组卵巢的重量都显著高于对照组1和2,但试验1和2组之间的差异不显著(P＞0.05);试验2组卵巢成熟卵泡发育个数和FSH的浓度显著高于试验1组和对照1和2组(P＜0.05);加强免疫第40天,试验1、2组的E2的浓度分别显著高于本试验组免疫前第0天,免疫后第20天的激素浓度;试验组与对照组在各个免疫试验时间LH的浓度在统计上差异不显著(P＞0.05).结果证明,应用重组抑制素真核表达质粒pcDNA-DPPISS-DINH-mC3d3(试验组2)免疫动物可以促进大鼠卵泡的发育,可提高血浆FSH、E2水平,为抑制素基因免疫大动物提供了试验依据.     

玉米赤霉烯酮中毒大鼠卵巢组织p53和NF-κB的表达

10周龄SD大鼠单剂量腹腔注射5mg/kg玉米赤霉烯酮(ZEA)玉米油溶液,分别于攻毒后3,6,12,24,48,72,96 h剖杀取卵巢组织,检测不同时间卵巢组织中p53和NF-κB的表达.病理组织学观察发现卵巢组织出现不同程度损伤,卵泡颗粒细胞凋亡.免疫组化结果表明试验组与对照组卵巢组织中均有p53和NF-κB的表达,并且随着时间的推进呈现动态变化.试验组p53在3,6,12h时表达量上调,12 h后表达量逐渐下降,各试验组与对照组相比较均差异显著(P＜0.05).NF-κB在3h表达量最高,而后表达量开始降低,各试验组与对照组相比较差异均显著(P＜0.05).大鼠玉米赤霉烯酮中毒可引起卵巢组织的病变及颗粒细胞凋亡,且p53和NF-κB在玉米赤霉烯酮中毒大鼠卵巢颗粒细胞凋亡发生过程中起着一定作用.     

醋酸铅对小鼠卵巢颗粒细胞凋亡基因p53、Bax、Bc1-2表达的影响

将40只未成年雌性昆明系小鼠随机分成3个处理组和1个对照组,每组10只.处理组小鼠分别连续2 d腹腔注射铅10、20、40 mg/kg(按体质量给药),对照组小鼠注射等体积的生理盐水.于注射后24、72 h分离卵巢,用原位末端标记法(TUNEL)测定卵巢颗粒细胞的凋亡率,同时用半定量RT-PCR方法检测凋亡基因p53、Bax、Bc1-2mRNA表达.结果表明,铅可促进颗粒细胞凋亡,且随剂量的增加和作用时间的延长,颗粒细胞中p53、Bax基因表达量逐渐增加,与对照组相比差异显著或极显著(P<0.05或P<0.01);而Bc1-2基因表达量则逐渐减少(P<0.05或P<0.01);表明铅可通过上调促细胞凋亡基因p53、Bax基因表达量,下调Bc1-2基因表达量,诱导卵巢颗粒细胞的凋亡.     

大鼠卵巢对不同超排处理的反应

将大鼠19只分为4组,第1、2、3组各5只,分别用PMSG 50 IU+HCG 60 IU、FSH50 IU+LH60 IU和P MSG50 IU连续处理3次;第4组4只(对照组),注射生理盐水0.5 mL.以上各组均采用腹腔注射,每次注射间隔时间24 h,最后一次注射后24 h剖检,测量卵巢体积、重量和排卵数.结果表明,不同试验组卵巢体积明显比对照组大(P<0.05),卵巢重量也有增加,但差异不显著(P<0.05).不同试验组都引起排卵,第1组排卵数最多,第2组最少,但差异不显著.     

醋酸铅对小鼠卵巢组织结构和卵巢颗粒细胞凋亡的影响

将40只20日龄雌性昆明系小鼠随机分成3个处理组和1个对照组,每组10只。给3个处理组小鼠分别连续2d腹腔按体质量注射醋酸铅10,20,40mg/kg,对照组小鼠注射等体积的生理盐水。于注射后24,72h分离卵巢,用原位末端标记法(TUNEL)测定卵巢颗粒细胞的凋亡率,研究卵巢组织结构及卵巢颗粒细胞凋亡的变化。结果显示,醋酸铅可使小鼠卵巢组织结构发生病变,加速卵巢颗粒细胞的凋亡,且凋亡率随着攻毒剂量的增加和时间的延长而升高,与对照组相比,差异极显著(P0.01);表明醋酸铅对小鼠卵巢具有毒性作用,可诱导卵巢颗粒细胞发生凋亡,并呈现一定的剂量-时间依赖关系。     

青春期前双酚A暴露对雌性大鼠生殖器官发育的影响

本研究旨在从毒性病理学角度探讨双酚A(BPA)暴露对青春期前雌性大鼠生殖器官发育的影响,为研究BPA雌激素样作用提供组织形态学依据。选用21日龄雌性大鼠,经不同浓度的BPA暴露后,检测大鼠脏器指数、血清雌二醇水平,观察子宫和卵巢形态结构。结果显示,BPA给予7 d后与对照组比较,BPA 180 mg/(kg·bw)组大鼠子宫和卵巢指数升高(P<0.05),血清雌二醇水平降低(P<0.05)。光镜观察发现,BPA试验组大鼠与对照组比较,子宫内膜增厚、内膜细胞形态改变,卵巢初级和次级卵泡数量增多。病理半定量分析结果表明,与对照组比较, BPA 180 mg/(kg·bw)组大鼠子宫内膜厚度、内腔面积及外腔直径、总卵泡数量有统计学差异(P<0.05)。表明BPA短期大剂量暴露可促进青春期前雌性大鼠子宫和卵巢发育,其作用存在明显的剂量依赖关系。     

大肠杆菌O111:B4内毒素对大鼠肝脏Fas蛋白表达的影响

为探讨大肠杆菌O111:B4内毒素(ET)对大鼠肝脏Fas蛋白表达的影响,本研究将48只SD大鼠随机分为试验组和对照组,试验组尾静脉注射ET,对照组尾静脉注射等体积无热源生理盐水;两组大鼠分别于注射后3h、4h、8h、12 h各迫杀6只,采集肝脏分别用于Fas蛋白表达的western blot检测和流式细胞术(FCM)检测.结果显示,试验组大鼠Fas蛋白的表达明显高于对照组(p＜0.01),并且呈上升趋势.该结果表明,ET能够有效上调大鼠肝细胞Fas蛋白的表达.     

DHEA诱导小鼠PCOS模型过程中性激素的变化规律

【目的】鉴于在多囊卵巢综合征(polycystic ovary syndrome, PCOS)发病机理和治疗方式上的诸多争议,以及使用人类PCOS材料进行研究的局限性,本研究通过构建PCOS小鼠模型以探究在模型构建过程中性激素水平的变化规律。【方法】皮下注射脱氢表雄酮(dehydroepiandrosterone, DHEA)诱导昆明白雌鼠产生PCOS样临床症状,通过结晶紫染色查看小鼠性周期是否发生停滞;利用HE染色的方式确定卵巢发育状况;利用ELISA技术调查建模过程中血清睾酮和雌二醇浓度的变化规律。【结果】使用结晶紫对小鼠阴道上皮细胞染色可准确区分小鼠各个性周期阶段;使用6 mg/100 g DHEA持续诱导20 d后,昆明白小鼠性周期循环发生了一定的停滞,且在建模过程中体重变化与芝麻油溶剂的加入呈显著相关(P<0.05),与DHEA处理无关;DHEA连续处理后可见卵巢中巨大囊状卵泡出现,血清睾酮水平出现显著升高(P<0.05);自PCOS模型构建的第5天起,血清睾酮水平显著上升(P<0.05),且维持到建模结束;而血清雌二醇水平出现了阶段性变化,在第10、15天...     

高频饮用牛奶和葡萄糖对雌性大鼠生殖机能的影响

选用22d断奶SD大鼠高频饮用牛奶或葡萄糖40d,分别记录各组动物的阴道开张时间和阴道黏液、每周日增重、卵巢及子宫所占体重百分比、血糖水平,收集卵巢进行组织学处理以观察卵泡发育情况,探讨高频饮用牛奶和葡萄糖对雌性大鼠初情期的影响.结果显示,奶组和糖组大鼠较对照组阴道开张时间来得早,预示初情期可能提前,而且,奶组和糖组大鼠的卵巢占体重百分比较对照组高(P＜0.05).牛奶组血糖水平比对照组高,但糖组与对照组血糖水平差异不显著.通过对卵巢进行石蜡切片、HE染色及卵泡计数,结果显示:奶组的闭锁卵泡、每张切片卵泡总平均数都比对照组多(P＜0.05),而葡萄糖组的黄体数比对照组少(P＜0.05).试验表明高频饮用牛奶和葡萄糖可对性成熟前雌性大鼠的生殖机能产生一定影响.     

高频饮用牛奶和葡萄糖对雌性大鼠生殖机能的影响

选用22d断奶SD大鼠高频饮用牛奶或葡萄糖40d,分别记录各组动物的阴道开张时间和阴道黏液、每周日增重、卵巢及子宫所占体重百分比、血糖水平,收集卵巢进行组织学处理以观察卵泡发育情况,探讨高频饮用牛奶和葡萄糖对雌性大鼠初情期的影响。结果显示,奶组和糖组大鼠较对照组阴道开张时间来得早,预示初情期可能提前,而且,奶组和糖组大鼠的卵巢占体重百分比较对照组高(P<0.05)。牛奶组血糖水平比对照组高,但糖组与对照组血糖水平差异不显著。通过对卵巢进行石蜡切片、HE染色及卵泡计数,结果显示:奶组的闭锁卵泡、每张切片卵泡总平均数都比对照组多(P<0.05),而葡萄糖组的黄体数比对照组少(P<0.05)。试验表明高频饮用牛奶和葡萄糖可对性成熟前雌性大鼠的生殖机能产生一定影响。     

母源性脱氢表雄酮对子代艾维因肉鸡脂肪代谢及肌肉品质的影响

本文以AA肉鸡为试验对象,研究母源性添加脱氢表雄酮(DHEA)对子代艾维因肉鸡脂肪代谢和肌肉品质的影响。将34周龄AA肉种鸡随机分为对照组(Con)、添加25 mg.kg-1DHEA的低剂量组(L)和50 mg.kg-1DHEA的高剂量组(H),2周后从各组收集种蛋进行孵化,随机选取180只出壳后的子代鸡,根据其母代饲料中添加DHEA的情况相应的分为对照组、低剂量组、高剂量组。饲喂至21 d宰杀,采集血清、肝脏、腹脂、左侧胸肌和腿肌样本进行分析。试验结果表明,与对照组相比母源性添加DHEA对子代肉鸡日采食量、日增体质量均无显著差异(P0.05),但母源性添加DHEA却可极显著地降低其料肉比(P0.01)。对子代公鸡而言,与对照组相比母源性添加高剂量的DHEA可显著地升高血清BG(P0.01)、NEFA(P0.05)和HDL-C(P0.05)的含量,极显著地降低肝脏组织中TG的含量(P0.01),但对血清TC、TG含量均无显著影响(P0.05);不同剂量的DHEA对其血清中T3、T4、GLU和Leptin的含量均无显著的影响(P0.05),但低剂量的DHEA却可显著地升高T3/T4值(P0.05)。对子代母鸡而言,与对照组相比母源性添加低剂量的DHEA可极显著地升高血清BG的含量(P0.01);高剂量的DHEA可极显著地升高血清TC、TG、NEFA和GLU的含量(P0.01),低剂量的DHEA可显著地升高HDL-C的含量(P0.05)和T4含量(P0.01),但却降低T3/T4值(P0.05)。母源性添加DHEA可显著地升高子代公鸡的胸肌率和腿肌率(P0.05),但对子代母鸡的胸肌率和腿肌率无显著影响(P0.05);同时母源性添加不同剂量的DHEA均可显著地降低腿肌肌纤维直径(P0.01),极显著地升高腿肌肌纤维密度(P0.01);高剂量的DHEA可极显著地降低胸肌肌纤维直径(P0.01),低剂量的DHEA可显著地降低胸肌肌纤维直径(P0.05),但不同剂量的DHEA均可极显著地升高胸肌肌纤维密度(P0.01)。结论提示,母源性添加DHEA可降低子代肉鸡脂肪的沉积和改善其肌肉品质。     

Effect of the gonadotrophins treatment on morphological alterations in ovary and peripheral plasma concentrations of steroid hormones in gilts

The present study was designed to examine the influence of gonadotrophins treatment on the ovarian morphology changes and plasma concentrations of steroid hormones in peripheral blood. The experiment was performed on sexually pubertal gilts (Large White x Landrace) of similar age (7-8 months) and body mass (100-110 kg) with two controlled subsequent estrous cycles. The animals were randomly divided into four groups: two control consisting of pigs with the luteal phase (n = 9, the 10th day of the estrous cycle) and the follicular phase (n = 6, the 20th day of the estrous cycle) and two experimental ones consisting of animals with both mentioned periods (n = 7 and n = 9) treated with gonadotrophins (PMSG and hCG). The gilts in the luteal phase were injected (s.c.) with gonadotrophins at a daily dose of PMSG 400 and hCG 200 IU from the 16th to the 27th day (the 6th day of the next estrous cycle). The gilts in the follicular phase, were injected with the same dose of gonadotrophins but from the 8th to the 19th day of the estrous cycle. Plasma concentrations of P4, A4, T, E1, E2 and metabolite of PGF2 alpha-PGFM were determined by radioimmunoassay (RIA) method. Injections of PMSG and hCG in both experimental groups produced several times enlarged: weight, size and volume of ovaries and alterations in a number of structural elements as compared with those found in the control animals. The morphological elements presented in ovaries: corpora haemorrhagica, corpora lutea, regular and atretic follicles and first of all cysts by distinctly differentiation thickness of the walls are characteristic for cystic ovarian degeneration. Plasma concentrations all determined hormones after gonadotrophins treatment in experimental groups were increased except E1 (insignificant decrease) in luteal phase as compared with those found in the control groups. Statistically significant increase (p < 0.001) in plasma concentrations of P4, A4, and T in both experimental groups and E2 (p < 0.001) in luteal phase were noted. In peripheral plasma concentrations increase of E1 and E2 in follicular phase of the estrous cycle were insignificant.     

Maternal exposure to low doses of bisphenol a has no effects on development of female reproductive tract and uterine carcinogenesis in Donryu rats

Effects of maternal exposure to low doses of bisphenol A (BPA), including those comparable with human exposure levels, on growth and development of the female reproductive system and uterine carcinogenesis in Donryu rats were investigated. Dams were administered BPA (0, 0.006 and 6 mg/kg/day) daily by gavage from gestation day 2 up to the day before weaning (postnatal day 21 at offspring). The serum levels of BPA were significantly elevated in the dams receiving 6 mg/kg/day, however, BPA levels in the milk of dams, and those in the serum and liver of offspring were similar between control and treated groups. The treatment did not exert any influences on uterine development including weight, gland genesis and estrogen receptor alpha expression, vaginal opening and gonadotropin secretion in the female offspring up to puberty. After maturation, no effects were evident with regard to estrous cyclicity in female offspring treated with BPA. In addition, the treatment had no effects on age-related morphological changes of the reproductive and endocrine organs and uterine carcinogenesis until 15 months of age. The results demonstrate that maternal exposure to BPA at levels comparable to human exposure did not have any effects on the female reproductive system of offspring in rats. In addition, BPA was also found in the serum, milk and liver of control dams and pups, and low levels of BPA were detected in drinking water and pellet diet. The present study showed that the experimental animals were also exposed to environmental BPA in the animal room.     

Thyroid hormones alter estrous cyclicity and antioxidative status in the ovaries of rats

To expand our understanding of the roles of thyroid hormones on female reproduction, we induced hypo‐ and hyper‐T rat models to investigate the roles of thyroid hormones on estrous cyclicity, as well as the antioxidative status in the ovaries of rats. In the current study, our data show that hypothyroidism (hypo‐T) and hyperthyroidism (hyper‐T) led to significantly reduced body weights and ovarain weights and delayed vaginal opening day. For hyper‐T, thyroxine (T4), tri‐iodothyronine (T3), progesterone (P4) and follicle‐stimulating hormone (FSH) were significantly increased, while estradiol (E2) and luteinizing hormone (LH) were significantly decreased. For hypo‐T rats, serum levels of total T4 and T3, E2, P4, FSH and LH were significantly increased, while concentrations of E2 and LH were significantly decreased. For ovary morphology, the numbers of secondary and antral follicles were significantly decreased with more atretic antral follicles and less corpora lutea in both hyper‐ and hypo‐T groups. Both hyper‐T and hypo‐T treatment significantly decreased the expressions of thyroid hormone receptor α1 in the ovary. Hypo‐T significantly reduced nitric oxide (NO), total NO synthase (tNOS), inducible NOS and constitutive NOS activities, but hyper‐T increased them. For antioxidative parameters, hypo‐T and hyper‐T treatment significantly increased malondialdehyde (MDA) contents. The activities of both glutathione peroxidase (GSH‐Px) and catalase (CAT) significantly decreased in the hypo‐T group but increased in the hyper‐T group. Total superoxide dismutase (T‐SOD) activity was significantly increased in the hyper‐T group. In summary, thyroid hormones alter estrous cyclicity and antioxidative status in the ovary of the rat may act through the NOS signaling pathway.     

Change Trends of Organ Weight Background Data in Sprague Dawley Rats at Different Ages

Organ weight is one of the most sensitive drug toxicity indicators, and its changes often precede morphological changes. So far, no background data about organ weight and its coefficient in SD rats at different weeks of age have been reported in China. The aim of this study was to summarize and analyze the change trends of organ weight and organ weight coefficients in SD rats at different weeks of age. The absolute of the weights of the brain, spleen, heart, lungs, liver, kidneys, adrenal glands and testes were increased in male SD rats from 13 to 78 weeks, and the weights of the brain, heart, lungs, liver, kidneys and especially the testes were decreased from 78 to 104 weeks. On the other hand, the absolute weight of the adrenal glands showed an increasing trend from 13 to 104 weeks. The absolute weight of the brain, spleen, heart, lungs, liver, kidneys, adrenal glands and ovaries showed an increasing trend from 13 to 104 weeks. A significant increase was observed in adrenal gland and ovary weights, whereas no obvious change trends were observed for the other organ weights mentioned above. It was surprising that the absolute of weight of the adrenal glands and organ-to-brain and organ-to-body weight ratios in female rats were significantly higher than those in males from 13 to 104 weeks. This study was the first to establish background data for organ weights in SD rats at different weeks of age and their reference ranges in line with the experimental animal status in China and to summarize their summarized their changes trend.     

Study on Acute and Sub-chronic Toxicity of Wu Jin Granules

In order to evaluate the toxicity of Wu Jin granules for the guidance of clinical treatment, the acute and sub-chronic toxicity were assessed in KM mice and Wistar rats, respectively.The results of acute toxicity test suggested that the LD₅₀ of Wu Jin granules was >40 g/(kg·BW), maximal tolerance dose was 160 g/(kg·BW), equivalent to 80 times of clinical dosage.In sub-chronic toxicity test, the growth and general behavior of the animals appeared normal.Compared with the control group, weight gain and feed consumption of Wistar rats in the treatment groups had no significant difference (P>0.05).In high dose group, serum bilirubin (T-BIL), total protein (TP), albumin (ALB), urea nitrogen (BUN) and creatinine (CREA) of female Wistar rats, whereas CREA levels and liver index of male Wistar rats were significant difference (P<0.05), and the differences in other indexes were not significant (P>0.05); Hematological indexes, biochemical indexes of blood and organ index of Wistar rats in low dose group and medium dose group were not significantly different compared to the control group (P>0.05).Pathological examination results showed that mild granular degeneration existed in liver of Wistar rats in high dose group, whereas appeared clear and normal organizational structure of liver in Wistar rats in other groups.Wu Jin granules could inhibit intake of free bilirubin and hepatic synthesis protein in high dosage, whereas this results were not observed in other groups.Thus, the Wu Jin granules were safe in clinical treatment.     

乌锦颗粒剂的急性毒性与亚慢性毒性试验研究

本研究旨在评价乌锦颗粒剂的毒性,为临床安全用药提供理论依据。试验分别以昆明小鼠和Wistar大鼠为研究对象,进行急性毒性试验和亚慢性毒性试验研究。急性毒性试验结果显示,乌锦颗粒剂的半数致死量(LD₅₀)>40 g/kg体重,最大给药量为160 g/kg体重,相当于临床用药量的80倍;在亚慢性毒性试验中,动物一般情况正常,试验组Wistar大鼠增重和饲料消耗量与对照组相比无显著差异(P>0.05);与对照组相比,高剂量组中雌鼠血清胆红素(T-BIL)、总蛋白(TP)、白蛋白(ALB)、尿素氮(BUN)和肌酐(CREA)及雄鼠CREA和肝脏指数均有显著差异(P<0.05),而其他指标与对照组相比差异均不显著(P>0.05);低剂量组和中剂量组Wistar大鼠血常规、血液生化指标和脏器指数与对照组相比差异均不显著(P>0.05);病理学检查发现高剂量组Wistar大鼠肝脏出现轻微颗粒变性,其他组Wistar大鼠组织结构清晰正常。结果表明,高剂量的乌锦颗粒剂能抑制肝脏对游离胆红素的摄入及蛋白质的合成;低剂量和中剂量乌锦颗粒剂此作用不明显。综合分析,乌锦颗粒剂临床用药是安全的。