Acute and Sub-Chronic Toxicity Evaluation of the Crude Methanolic Bark Extract of Bridelia micrantha (Hochst.) Baill. (Phyllanthaceae) and Its Fraction

Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F6 was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F6 induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 was estimated to be more than 2000 mg/kg.

Evaluating the safety of forsythin from Forsythia suspensa leaves by acute and sub-chronic oral administration in rodent models

Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice,Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0,540,1 620,and 6 480 mg/kg in SD rats.Results: In the acute toxicity study,mortality was not observed after 14 days,In addition,clinically relevant adverse effects,or variations in body weight or food consumption were not observed,Similarly,after 30 days in the sub-chronic toxicity study,no mortality or significant toxicological effects such as decreased food consumption,body weight,biochemical parameters and vital organs etc,were noticed,Conclusion: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration,and therefore is suitable for further development and applications.

Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs

Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.

Effects of Sub-chronic Aluminum Exposure on Renal Pathologic Structure in Rats

A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg aluminum chloride （AlCl3） per kilogram body weight in drinking water for 120 days. Kidney coefficient and aluminum （Al） concentrations in blood and kidney were determined, and renal autopsy and histological changes were observed. The results showed that kidney coefficient in all Al-treated groups were obviously lower than that in GC （P〈0.01） and there was a dose-effect relationship. The kidneys were solid, lusterless and pale brown with white necrosis point on surface. Under electron microscope, renal cortex became thin, the renal tubule was narrowed and the epithelium dissolved; the renal glomerulus became atrophied and the glomerular became vasodilator. The Al concentrations in blood and kidney were higher in all Al-treated rats than those in GC （P〈0.01）, and there was a dose-effect relationship. The results indicated that sub-chronic Al exposure could lead to Al accumulation in kidney, restrain the development of kidney and cause the pathologic damage in rats.

Effects of Sub-chronic Intoxication of 1,8-cineole on Blood Biochemical Indexes of Mice

[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.

Effects of Sub-chronic Aluminum Exposure on Renal Structure in Rats

To investigate the effects of aluminurn （Al） exposure on renal structure of rats, 60 Wistar rats were randomly divided into four treatment groups and were orally exposed to 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg· kg^-1 BW AlCl3 in drinking water for 120 days. The body weight of different rats was recorded, the kidney pathologic structure and the ultrastructure were observed. The results showed that the body weight of different rats was markedly lower in Al-treated rats than those in GC （P〈0.05; P〈0.01）. After masson staining, the collagen was deposited in the renal interstitium and aggravated with Al dose increases in Al-treated rats. Under electron microscope, the infolding of the plasma membrane was slight swollen, the mitochondrion was abundant with different sizes, the mitochondrion cristae was fused, the microvillus was swollen and fused in GH. Our findings indicated that sub-chronic A1 exposure slowed the weight of rats and caused the kidney pathologic damage in rats.

Sub-chronic Toxicity Test of Tephrosia canadida DC. in Mice

[ Objective] To observe sub-chronic toxicity of Tephrosia canadida DC. in mice and thus to evaluate their safety to be used as protein feed resources. [ Methed]Sixty-four 6-week-old healthy Kunming mice weighing about 25 g were randomly divided into four groups （ n = 16）, half male and half female. Mass ratios of basic diet to leaf meal of Tephrosia canadida DC. in group A, group B, group C and group D were 10：0, 4：1, 3：2 and 2：3, respectively. After 35-d feeding, the effects of Tephrosia canadida DC. on growth, blood and organs of mice were observed. [ Resultl Dudng the trial, all mice had normal activities, and no death and no abnormal blood index were observed. All organs of the mice in the experimental groups had no visible pathological lesion, and organ indexes had no significant difference between the experimental groups and the control group. Except that slightly abnormal histological changes appeared in liver and kidney of the mice in the group C and D, no histological change was ob- served in other organs of the experimental mice. [ Conclusion] Tephrosia canadida DC. have no adverse effects on mice, which provides a refer- ence for research about their safety in feed of other animals.

Sub-chronic Toxicity of Defoamer Used in Seawater Desalination

Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high(0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. Results The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase(P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin(P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups(P < 0.05). All dose groups showed significant induction of alkaline phosphatase(P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. Conclusion Long‐term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.

Sub-chronic(Ninety Days)Toxicity Study of Hydroethanolic Leaf Extract of Datura stramonium L.in Rodents

Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the effects of 90 days of oral administration of Datura stramonium(DSE)leaf extract in Rats.Methods:In the oral acute toxicity study,mice were treated with a single oral gavage of DSE at 500,1000,and 2000 mg·kg^(-1)/d,po and observed for signs of acute toxicity for 14 days.In the sub-chronic study,rats were randomized into four Groups(A-D).Group A received distilled water(10 mL·kg^(-1),po)while groups B-D received DSE(10,50 and 250 mg·kg^(-1)/d,po,respectively)orally for 90 days uninterrupted.Animals were weighed weekly,with food and water measured daily and relevant parameters assayed at the end of the 90days administration.Results:In acute toxicity studies,oral administration of up to 2 g·kg^(-1)/d,po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days.In the 90days studies,DSE(250 mg·kg^(-1)/d,po)decreased the body weight,brain weight,and food intake in female rats.DSE(10-250 mg·kg^(-1)/d,po)increased the red blood cell(RBC),packed cell volume(PCV)and hemoglobin(Hb)in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the triglycerides(TG),cholesterol and low-density lipoprotein(LDL);and decreased HDL in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the white blood cells(WBC)and platelets in female rats.DSE(10-250 mg·kg^(-1)/d,po)decreased the alkaline phosphatase(ALP)and alanine transaminase(ALT)in both studies.Serum urea level was decreased in both sexes.DSE(250 mg·kg^(-1)/d,po)decreased male rats’serum sodium ion levels.Liver,brain,testes and kidney showed severe lesions at 250 mg·kg^(-1)/d,po of the extract.Conclusion:D.stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration.How-ever,prolonged use,especially at high doses,could cause Liver,brain and kidney toxicities;and abnormal lipid metabolism.

Acute and Sub-chronic Toxicity of Tetrandrine in Intravenously Exposed Female BALB/c Mice

Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was calculated in mice using Dixon＇s up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET（30, 90 and 150 mg/kg） each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result： LD_（50） was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET（P〉0.05）. In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group（P〉0.05）, however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions： The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.

羧甲基茯苓多糖阻遏亚慢性应激诱发的抑郁样行为

探讨羧甲基茯苓多糖在缓解亚慢性应激诱发的抑郁样行为中的作用。通过连续2周温和不可预知应激,在造模的后7 d,每日分别用0.1、0.2、0.4 g/kg羧甲基茯苓多糖干预模型小鼠。采用16S rRNA高通量测序法分析小鼠肠道菌群组成,ELISA法测定血清中炎性因子水平,分别用LC-MS和GC-MS法测定粪便中神经递质和短链脂肪酸含量,并通过强迫游泳、高架十字迷宫和旷场实验测定小鼠抑郁样行为。结果表明,与模型组相比,低、中剂量的羧甲基茯苓多糖均能不同程度改善抑郁样行为,并改变肠道菌群的组成,降低革兰氏阴性菌的相对丰度(P<0.05);中剂量能够显著降低血清中IL-6 (P<0.01)和IL-2 (P<0.05)的水平;各剂量可通过调节Lactobacillus和Parabacteroides的丰度,显著下调异戊酸、NE、5-HT以及Ach的含量,从而减少IL-6的过量释放。综上,羧甲基茯苓多糖可通过调节肠道菌群组成,抑制肠源性异戊酸、NE、5-HT以及Ach的释放,降低抑郁症相关的炎性因子IL-6和IL-2的水平,从而有效阻遏亚慢性应激诱发的抑郁样行为。

聚β-胡萝卜素聚合物的急性毒性试验、亚慢性毒性试验和致突变性试验

本试验旨在通过小鼠急性毒性试验、大鼠亚慢性毒性试验和小鼠致突变性试验对聚β-胡萝卜素聚合物进行安全性评价。急性毒性试验:将50只昆明小鼠随机分为5组,每组10只。测定聚β-胡萝卜素聚合物的半数致死量(LD_(50))和95%置信区间。亚慢性毒性试验:将80只无特定病原体(SPF)级SD大鼠随机分为4组,每组20只。低、中高剂量组分别灌胃100、250和500 mg/kg BW的聚β-胡萝卜素聚合物,对照组灌胃等体积的植物油,连续灌服30 d。测定大鼠生长性能、血液生理指标、血清生化指标、脏器指数及组织病理学。致突变性试验:将50只昆明小鼠随机分为5组,每组10只。依据本试验得出聚β-胡萝卜素聚合物的LD50,低、中、高剂量组分别灌胃282.5、565.0和1130.0 mg/kg BW的聚β-胡萝卜素聚合物,阴性对照组灌胃等体积的植物油,阳性对照组腹腔注射0.4 mL/kg环磷酰胺。测定嗜多染红细胞/红细胞比值和嗜多染红细胞微核率。结果表明:1)急性毒性试验中,聚β-胡萝卜素聚合物的LD_(50)为2260 mg/kg BW,95%置信区间为2067~2470 mg/kg BW。2)亚慢性毒性试验中,试验期间内大鼠精神食欲等状况良好。与对照组相比,低、中、高剂量组的雄性大鼠和高剂量组的雌性大鼠末重、平均日增重、平均日采食量极显著升高(P<0.01),料重比极显著降低(P<0.01)。中剂量组的雄性大鼠红细胞压积显著低于低剂量组(P<0.05),各组之间大鼠的其他血液生理指标和血清生化指标均无显著差异(P>0.05)。中、高剂量组的雌性大鼠肾脏指数显著低于对照组和低剂量组(P<0.05),各组之间大鼠的脏器重和其他脏器指数均无显著差异(P>0.05)。组织病理学检查表明各组大鼠心脏、肝脏、脾脏、肾脏、肺脏无明显病理变化。3)致突变性试验中,与阴性对照组相比,阳性对照组的雄性、雌性小鼠的嗜多染红细胞微核率极显著增加(P<0.01),低、中、高剂量组的雄性、雌性小鼠的嗜多染红细胞微核率均差异不显著(P>0.05)。由此可见,聚β-胡萝卜素聚合物无明显急性毒性、亚慢性毒性和致突变性。聚β-胡萝卜素聚合物可以提高大鼠的生长性能,可作为一种安全的饲料添加剂进一步开发利用。

新生大鼠啶虫脒亚慢性暴露致成年后神经系统毒性的研究

观察新生大鼠啶虫脒(acetamiprid,ACE)慢暴露对成年后神经行为、大脑皮质与海马的影响。选择出生一周的雄性Sprague-Dawley(SD)大鼠18只,随机分为对照组(Control)、ACE-15组(15 mg·kg^(-1)·d^(-1))、ACE-40组(40 mg·kg^(-1)·d^(-1)),每组6只。ACE暴露组灌胃干预9周,期间每周检测体质量。采用开放旷场实验(OFT)、Morris水迷宫(MWM)检测大鼠行为学变化;采用试剂盒检测大脑皮质和海马组织中丙二醛(MDA)和超氧化物歧化酶(SOD)水平;采用Western Blot法检测白细胞介素IL^(-1)β、IL^(-1)0蛋白表达量;采用苏木精-伊红(H&E)染色法检测大脑皮质和海马组织病理学改变;采用Nissl染色法检测大脑海马DG、CA3区神经元变化。OFT结果显示,与对照组相比,ACE暴露组大鼠在中央区运动距离和时间均减少。MWM结果显示,定位巡航期间,暴露组逃逸潜伏期时间增加,目标象限停留时间减少。空间探索期间,ACE-40组跨平台次数减少,目标象限内游泳速度降低。暴露组大鼠脑皮质和海马组织中MDA浓度增高;暴露组大鼠脑皮质SOD活性降低,海马组织SOD活性增高。Western Blot结果显示,与对照组相比,暴露组大鼠皮质和海马组织中IL^(-1)β表达量增高;IL^(-1)0表达量降低。H&E结果显示,ACE-40组海马DG、CA3区神经元出现排列紊乱、层数减少和轮廓模糊。Nissl染色结果显示,暴露组大鼠海马DG、CA3区神经元数量减少,尼氏小体减少。以上结果表明,新生大鼠ACE亚慢性暴露能够导致成年后神经行为变化,可能与脑皮质和海马组织的氧化应激与炎症有关。

白果中内源性组分吡哆醇对大鼠的急性和亚慢性毒性评价

考察了白果中内源性组分吡哆醇对SD大鼠的急性和亚慢性毒性。在急性毒性试验中,根据《食品安全国家标准GB15193.3-2014》中的限量法对SD大鼠单次灌胃5000 mg·Kg^(-1)吡哆醇,测试其半致死量(LD 50)。在亚慢性毒性试验中,根据《食品安全国家标准GB15193.22-2014》进行实验,分别以3.15、15.8、31.5 mg·Kg^(-1)的吡哆醇连续灌胃SD大鼠28 d,观察大鼠生理状况及体重变化情况,并对大鼠的脏器指数、血清生化指标、病理组织切片和氧化应激能力进行分析。结果表明,急性经口毒性试验中,雌雄大鼠的LD 50均大于5000 mg·Kg^(-1),并且给药组雌雄大鼠的心脏几乎没有受到影响,肾脏受到轻度影响,肝脏受到一定的损伤,出现肝细胞点状坏死等。亚慢性经口毒性试验中,与对照组雌雄大鼠相比,中、高剂量组雌雄大鼠血清中谷丙转氨酶、谷草转氨酶含量均显著升高(P<0.05或P<0.01),高剂量组雌性大鼠血清中总胆红素含量显著升高(P<0.05);病理组织切片分析结果表明,三个给药组雌雄大鼠的心脏和肾脏几乎没有受到影响,但中、高剂量组雌雄大鼠的肝脏受到一定的损伤,出现肝细胞点状坏死等;氧化应激实验分析结果表明,与对照组雌雄大鼠相比,中剂量组雌雄大鼠肝脏中丙二醛含量显著升高(P<0.05),高剂量组雌雄大鼠肝脏中诱导型一氧化氮合成酶含量显著升高(P<0.01),进一步证实了中、高剂量组雌雄大鼠的肝脏受到了损伤。

砷对雄性大鼠睾丸组织AQP-8及survivin蛋白表达的影响

[目的]研究亚慢性砷中毒对大鼠睾丸组织AQP-8及survivin蛋白表达的影响。[方法]将40只健康成年清洁级SD雄性大鼠随机分为对照组以及低、中、高剂量砷染毒组,每组10只;采用自由饮水方式染毒,低、中、高剂量染毒组饮水中亚砷酸钠浓度分别为2.4、12.0、60.0 mg/L,连续染毒15周,对照组饮用蒸馏水;染毒试验结束后,对各组大鼠进行精子计数,计算精子存活率;制备睾丸组织切片进行病理学观察;利用免疫组化及Western blotting法测定大鼠睾丸组织中AQP-8及survivin蛋白的表达水平。[结果]与对照组相比,中、高剂量染毒组大鼠精子计数与精子存活率均降低,且差异显著(P<0.05)。低剂量染毒组大鼠生精小管无明显变化;中剂量染毒组大鼠生精上皮层数减少,小管间隙增宽;高剂量染毒组大鼠部分生精小管出现基膜溶解,生精上皮细胞层次紊乱,细胞间隙增大,间质出现水肿、渗出。免疫组化分析结果显示,AQP-8蛋白主要表达于各级生精细胞的细胞膜和精子细胞,与对照组相比,各剂量染毒组大鼠睾丸组织中AQP-8阳性细胞平均光密度值显著(P<0.05)升高;survivin蛋白主要表达于次级精母细胞和精子细胞的胞浆,与对照组相比,各剂量染毒组大鼠睾丸组织中survivin阳性细胞平均光密度值显著(P<0.05)降低。Western blotting分析结果显示,对照组和各剂量染毒组大鼠睾丸组织中均存在AQP-8及survivin蛋白的表达;与对照组相比,低、中、高剂量染毒组AQP-8蛋白表达量显著(P=0)增加,survivin蛋白表达量显著(P=0)降低。[结论]砷暴露使睾丸组织AQP-8蛋白表达量增加,survivin蛋白表达量下降,这可能是导致其雄性生殖毒性效应的机制之一。

荚膜甲基球菌蛋白的急性毒性和亚慢性毒性研究

为评价荚膜甲基球菌蛋白(MBM)急性与亚慢性毒性,进行在大、小鼠的急性经口毒性试验和大鼠的90 d亚慢性毒性试验。急性毒性试验将大、小鼠各40只,分别随机分为对照组和给药组,给药组剂量为10 g/kg·bw,对照组灌胃相等体积的溶媒。给药后连续观察14 d,于第15天进行大体剖检。亚慢性毒性试验将80只大鼠,随机分为高、中、低剂量组和对照组,分别饲喂添加5%、2.5%和1%MBM的饲料和空白饲料,连续90 d。试验期间每天进行观察,每周记录体重、摄食和饮水量,于试验第45天和90天每组随机采血10只大鼠后进行病理学检查并摘取指定脏器计算脏器系数,血液用于血液学和血液生化检查。结果显示:急性毒性试验中除因操作不当导致一只小鼠死亡外,观察期内未见中毒症状与动物死亡,大体剖检各脏器组织均无异常;亚慢性毒性试验期间除计划剖检外动物均存活且无中毒症状,虽有个别指标与对照组存在统计学差异,但与MBM毒性无关,病理学检查亦未见病变。结果表明MBM在大、小鼠LD50均≥10 g/kg·bw;添加5%MBM于饲料中未观察到明显的有害作用,无作用剂量至少达到3100 mg/kg·bw。

芜湖市5G^(+)中医治未病健康管理服务云平台的构建

目的慢性疾病已成为中国人民群众健康的主要威胁,笔者提出基于5G^(+)中医综合诊断系统构建芜湖市5G^(+)中医治未病健康管理服务云平台(简称健康管理服务云平台),解决基层医疗卫生服务资源不足等问题。方法基于圣美孚中医综合诊断系统和5G^(+)技术,云平台构建以三级医院为诊断中心、基层医疗机构为采集中心的中医医联体云平台体系,主要功能包括视频会诊、远程联合门诊、双向转诊、远程教学等。在芜湖市选择1家区县级中医院、1家社区卫生服务中心、1家乡镇卫生院作为示范基地,构建健康管理服务云平台并实施应用和评估。选择2018年10月至2023年1月在芜湖市中医医院、南陵县中医医院、芜湖市镜湖区镜湖新城社区卫生服务中心、南陵县何湾镇中心卫生院等符合亚健康人群、糖尿病、慢性肝病等标准155例,其中男性76例,女性79例;年龄49~74岁,平均年龄61.94岁;慢性肝病56例,糖尿病99例。使用健康管理服务云平台对患者进行健康管理。调查医生和服务对象的满意度。结果健康管理服务云平台功能有建立电子档案、接诊功能、干预功能、远程诊疗功能、数据统计功能、沟通功能。对接诊155例次,根据疾病的复杂程度和患者需求完成转诊18次。用于医生的调查问卷发放15份,收回15份;医生满意率60%~100%。服务对象的调查问卷35份,收回29份;服务对象满意率75.90%~100.00%。结论该平台的构建能够形成上下联动、智能化、个性化的中医健康管理服务体系,实现了县级中医院对社区卫生服务中心、镇卫生院进行数据访问和远程指导及对辖区内居民慢性疾病健康状态的监控和管理。根据未病先防、既病防变的理论结合慢性疾病诊疗的特点,围绕患者预防、医疗、康复等不同需求提供科学高效的诊疗服务,为慢性疾病的防控提供了多元化手段。

Caspase-9蛋白在亚慢性砷染毒大鼠睾丸间质细胞中的表达研究

[目的]探讨亚慢性砷染毒对大鼠睾丸间质细胞Caspase-9蛋白表达的影响。[方法]将40只健康成年清洁级SD雄性大鼠随机分为4组,分别为对照组以及低、中、高剂量染毒组,每组10只。采用自由饮水方式进行染毒,低、中、高剂量染毒组亚砷酸钠的染毒剂量分别为2.4、12、60 mg/L,对照组给予生理盐水,染毒试验持续14周。染毒试验结束后,检测大鼠外周血白细胞数量;采用ELISA法检测大鼠血清TNF-α及IL-1的浓度;利用透射电镜观察大鼠精子的超微结构;应用免疫组化法检测大鼠睾丸间质细胞Caspase-9蛋白的表达定位及表达水平。[结果]与对照组相比,中、高剂量染毒组大鼠血清中TNF-α、IL-1浓度及白细胞计数均显著(P<0.05)升高。透射电镜下,对照组精子顶体结构完整,厚度及染色均匀;低剂量染毒组可见精子胞膜肿胀,核染色质较均匀;中剂量染毒组精子顶体与核分离,胞膜肿胀;高剂量染毒组精子尾部中断,轴丝排列紊乱。免疫组化法分析表明,Caspase-9蛋白主要表达于睾丸间质细胞的细胞质,表达信号呈棕褐色;与对照组相比,各剂量染毒组大鼠睾丸组织内Caspase-9蛋白的表达水平均显著(P<0.05)升高。[结论]睾丸间质细胞Caspase-9蛋白表达水平升高可能是亚砷酸钠致雄性大鼠慢性生殖毒性的机制之一。

雷公藤甲素亚慢性中毒对昆明种小鼠肾脏及睾丸的影响

为了观察雷公藤甲素肾脏及睾丸的毒性影响 ,80只昆明小鼠随机分成 3个实验组和 1个对照组。6 0 d内 3个实验组的小鼠每 48h腹腔注射雷公藤甲素一次 (A组 :0 .0 2 5 mg/ kg,B组 :0 .0 5 mg/ kg,C组 :0 .1mg/ kg)。结果显示 :肾脏病变除肾小管上皮细胞变性、坏死外 ,肾小管管腔内出现蛋白管型 ,最后处死的所有实验组动物的 90 %以上肾小球囊壁壁层上皮不同程度地增生 ,BUN检测结果表明 ,B组和 C组均显著性升高 (P<0 .0 5 ) ,提示有发展成肾功能衰竭的趋势。说明甲素对小鼠的肾损害可能是亚慢性中毒者的主要死亡原因之一。睾丸病变明显 ,表现为睾丸萎缩 ,脏器系数降低 ,各级生精细胞变性、坏死 ,数量减少 ,其中以精子、精子细胞和次级精母细胞最敏感 ,实验结果还表明甲素对睾丸具有蓄积毒性。提示雷公藤在抗生育作用中 。

人参叶口服液对大鼠的亚慢性毒性试验

将Wistar大鼠随机分为4组,3个剂量组(以人参皂苷计)分别按40、80、160 mg/kg体重给大鼠灌胃,对照组给予同体积生理盐水,1次/d,连续28 d,记录大鼠毒副反应。停药后继续观察14 d,测试大鼠体重、血液学指标、血液生化学指标、脏器指数。结果表明,各剂量组大鼠与对照组比较,给药期与恢复期的体重增长,血液学指标、血清生化指标、脏器指数均无显著性差异(P>0.05)。试验结果表明,人参叶口服液连续给药28 d,大鼠未出现无不良反应,停药14 d后亦未出现迟发性不良反应。