首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 93 毫秒
1.
目的 研究樟芝多糖通过CD4+CD25+Foxp3+调节性T细胞(Treg)的调控对小鼠非酒精性脂肪性肝病(NAFLD)的保护作用。方法 高脂饮食构建小鼠NAFLD模型,设置对照组、模型组、低剂量组、高剂量组。樟芝多糖干预1~4周中每周流式细胞术检测外周血Treg细胞的比例,谷丙转氨酶(ALT)、谷草转氨酶(AST)的表达,外周血中转化生长因子β(TGF-β)、白介素-6(IL-6)的表达。樟芝多糖干预4周后,小鼠处死,取肝脏进行油红染色,Western blot法检测肝组织中TGF-β和Foxp3、Smad3蛋白的表达,RT-qPCR检测IL-6、TGF-β、Foxp3、Smad3的mRNA表达。结果 高脂饮食喂养4周后成功构建NAFLD小鼠模型,且模型组中Terg比例显著低于对照组(P<0.05),樟芝多糖干预后Treg比例相比模型组显著增高(P<0.05),小鼠肝功能得到显著改善,外周血中TGF-β表达上调、IL-6的表达下调,肝组织中TGF-β和Foxp3、Smad3蛋白和mRNA均上调,而IL-6的mRNA表达下调。结论 樟芝多糖可以通过Treg和TGF-β-Smad3信号对NAFLD起到保护作用,作用机制和免疫改善有关。  相似文献   

2.
目的 探讨注射用益气复脉(冻干)(YQFM)对失血性休克大鼠的药效作用。方法 通过股动脉放血的方法建立失血性休克大鼠模型,随机将造模成功的大鼠分为模型组、肾上腺素(10 μg·kg-1盐酸肾上腺素注射液)组、YQFM低和高剂量(232.2、464.3 mg·kg-1,464.3 mg·kg-1为临床等效剂量)组、联合给药(肾上腺素10 μg·kg-1+YQFM 464.3 mg·kg-1)组,每组10只,假手术组只切口不放血。给药结束后,观察给药3 h内大鼠存活情况;使用八通道无创血压仪监测造模前、造模后、给药3 h后的收缩压;酶联免疫(ELISA)法检测各组大鼠血清中肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和超氧化物歧化酶(SOD)水平。结果 造模后大鼠的平均动脉压均维持在30~40 mm Hg,表明造模成功。假手术组及各给药组大鼠在3 h内全部存活,模型组死亡3只,存活率为70%,平均生存时间为(166.00±23.66) min。各组大鼠的基础血压无显著性差异,模型组和各给药组大鼠造模后收缩压显著降低,与假手术组比较差异显著(P<0.001);与模型组比较,给药3 h后各给药组收缩压均显著升高(P<0.001),联合给药组升压效果最好。与模型组相比,肾上腺素组血清CK-MB、LDH、ALT、AST水平均显著下降(P<0.01); YQFM低剂量组LDH、ALT、AST水平显著降低(P<0.05); YQFM高剂量组与联合给药组血清CK-MB、LDH、ALT、AST水平显著降低,SOD水平显著升高(P<0.05、0.01、0.001),联合给药对血清生化指标的改善作用最好。结论 YQFM可以明显提高失血性休克大鼠的收缩压水平,改善血清中相关生化指标水平,且与肾上腺素联用具有一定的协同作用。  相似文献   

3.
彭峰  林隆  詹璐 《中国现代应用药学》2023,40(15):2100-2107
目的 探究桔梗总皂苷是否通过介导Notch通路对哮喘Th17/Treg平衡进行调控。方法 48只BALB/c小鼠随机分为正常对照组,模型组,桔梗总皂苷低、中、高剂量组(15,30,60 mg·kg-1)和地塞米松组,每组8只。雾化吸入卵清蛋白建立小鼠哮喘模型,药物干预8周后,测定小鼠气道高反应性。取材支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)细胞计数、ELISA检测、HE、PAS及Masson染色,流式细胞术检测小鼠肺组织Th17、Treg细胞百分比及Th17/Treg比值变化情况,qPCR检测小鼠肺组织Notch1、Jagged1、RORγt、Foxp3表达水平,Western blotting检测小鼠肺组织中Notch1、Jagged1、Hes1及RORγt、Foxp3、IL-10、IL-17蛋白表达情况。结果 与模型组相比,桔梗总皂苷中、高剂量组小鼠气道阻力减小,BALF中炎性细胞数量及炎性因子IL-4、IL-5、IL-13含量降低,血清IL-17、IL-6、IgE含量降低,BALF中INF-γ及血清中IL-10含量水平显著升高(P<0.05或P<0.01)。HE、PAS及Masson结果显示,桔梗总皂苷高剂量组及地塞米松组能够显著缓解炎性细胞浸润及支气管膜破坏情况,减少杯状细胞增生,同时减轻组织胶原纤维散出程度。流式细胞术结果显示,桔梗总皂苷中、高剂量组Th17细胞数量及Th17/Treg占比均显著减少,Treg细胞数量显著增加(P<0.05或P<0.01)。qPCR及Western blotting结果显示,桔梗总皂苷给药处理后小鼠肺组织Notch1、Jagged1、RORγt mRNA及Notch1、Jagged1、Hes1、RORγt、IL-10、IL-17蛋白的表达水平均显著降低,Foxp3 mRNA及Foxp3蛋白的表达水平显著升高(P<0.05或P<0.01)。结论 桔梗总皂苷能够介导Notch通路对哮喘Th17/Treg平衡进行调控,从而起到减轻气道炎症,抑制哮喘发作的作用。  相似文献   

4.
目的 探讨青蒿琥酯自微乳对非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)模型大鼠的保护作用及作用机制。方法 高脂饲料诱导10周建立大鼠NAFLD模型。SD大鼠分为7组:正常组,模型组,青蒿琥酯组,多烯磷脂酰胆碱组,青蒿琥酯自微乳高、中、低剂量组。给药10周后处死所有动物,检测各组大鼠血清ALT、AST、TG、TC、TNF-α和IL-10指标水平。结果 与模型组比较,各药物治疗组(除低剂量组外)均能明显改善血清ALT、AST、TG、TC、TNF-α和IL-10指标水平(P<0.05或<0.01)。结论 青蒿琥酯自微乳通过调节脂质代谢、抑制炎性细胞因子的释放,减轻肝细胞的损伤,从而对高脂饮食诱导的NAFLD模型大鼠具有一定的保护作用。  相似文献   

5.
板蓝根水提物对糖尿病大鼠早期肝损伤的影响   总被引:2,自引:2,他引:0  
目的 研究板蓝根水提物(water extract of Radix Isatidis,WERI)对糖尿病大鼠肝功能的影响。方法 采用链脲佐菌素诱导Wistar大鼠糖尿病模型,随机分为模型组、罗格列酮组(0.3 mg·kg-1)、WERI高、中、低剂量组(100,50,25 mg·kg-1),并设正常对照组,均采用灌胃给药。4周后,检测各组大鼠空腹血糖(FBG)、空腹胰岛素(FINS)、肝系数、谷丙转氨酶(ALT)、谷草转氨酶(AST)、游离脂肪酸(FFA)和血清脂联素(ADP),并观察大鼠肝脏组织病理形态学变化。结果 与正常对照组比较,模型组大鼠FBG、FINS、肝系数、ALT、AST、FFA水平均显著升高(P<0.05或P<0.01);血清ADP含量显著降低(P<0.05)。与模型组比较,WERI高剂量组大鼠FBG、FINS、肝系数、ALT、AST、FFA水平均显著降低(P<0.05或P<0.01),血清ADP含量升高(P<0.05);罗格列酮组与WERI高、中、低剂量组大鼠肝脏病理形态均显著改善。结论 WERI对糖尿病大鼠的肝功能具有保护作用。  相似文献   

6.
目的 探讨水飞蓟宾对高脂诱导的非酒精性脂肪肝(NAFL)模型大鼠的调脂保肝作用。方法 采用ig高脂乳剂配合高脂饲料制备大鼠NAFL模型,持续4周,对照组给予生理盐水和普通饲料。模型大鼠随机分为模型组、辛伐他汀(阳性药,1.8 mg/kg)组和水飞蓟宾低、中、高剂量(18.9、37.8、75.6 mg/kg)组,第5周在继续造模的基础上ig给药,每天1次,持续8周。末次给药后,称取肝脏质量并计算肝系数;HE染色观察肝组织病理形态;腹主动脉取血,分离血清,试剂盒法检测三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)水平。结果 连续治疗8周后,与对照组比较,水飞蓟宾高、中剂量均可明显改善肝组织脂肪变性程度;各剂量组肝系数均显著下降(P<0.05、0.01);各剂量组均显著降低血清TC、TG、AST、ALT水平(P<0.05、0.01);高、中剂量组显著降低LDL、升高HDL水平(P<0.01)。结论 水飞蓟宾对NAFL大鼠发挥治疗作用,其作用可能与降脂、保肝有关。  相似文献   

7.
目的 研究胡黄连苷Ⅱ对四氯化碳(CCl4)诱导的大鼠急性肝损伤的保肝和利胆作用。方法 保肝作用和利胆作用研究各选取60只健康SD大鼠,均随机分为6组:对照组、模型组、溶剂对照组和胡黄连苷II低、中、高剂量(2.5、5.0、10.0 mg·kg-1)组,除对照组外,其余5组大鼠分别1次性ip给予CCl4油溶液(50%橄榄油、2 mL·kg-1)制备急性肝损伤模型。保肝作用研究:在造模后3、24和48 h ig给药1次,对照组和模型组ig给予等体积生理盐水,溶剂对照组ig给予等体积溶剂,试剂盒法检测血清中丙氨酸氨基转移酶(ALT)、天氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总胆红素(TBIL)、总胆汁酸(TBA)、肿瘤坏死因子-α (TNF-α)、白细胞介素-8 (IL-8)及白细胞介素-6 (IL-6)水平和肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽S转移酶(GST)、谷胱甘肽(GSH)及谷胱甘肽过氧化物酶(GSH-Px)水平; HE染色观察肝组织病理改变。利胆作用研究:大鼠造模12 h之后进行胆管插管,并通过十二指肠给药,给药前及给药后30、60、90及120 min分别记录胆汁流量。结果 与模型组比较,胡黄连苷II能显著降低血清中肝功能生化指标ALT、AST、ALP、TBA和TBIL水平(P<0.01);显著降低大鼠肝脏MDA水平,并显著增加肝脏SOD、CAT、GSH、GST及GSH-Px水平(P<0.01);显著降低血清TNF-α、IL-6及IL-8水平(P<0.01),且呈剂量相关性。胡黄连苷II各剂量均可不同程度减轻模型大鼠肝脏病变范围与程度。与模型组比较,各给药后时间点胡黄连苷II均可显著增加胆汁流量(P<0.01),且呈剂量相关性。结论 胡黄连苷II能显著缓解CCl4诱导的大鼠急性肝损伤并增加胆汁流量。  相似文献   

8.
目的 探讨绞股蓝总苷对慢性脑缺血大鼠海马神经元的保护作用及可能机制。方法 选取50只健康SD大鼠,♂,随机分为假手术组、模型组和绞股蓝高、中、低剂量组,每组10只。通过双侧颈总动脉永久性结扎法,建立慢性脑缺血模型,造模手术后24 h,绞股蓝总苷高、中、低剂量组大鼠分别灌胃100,50,25 mg·kg-1的绞股蓝总皂苷,每日1次,连续8周。Morris水迷宫法检测大鼠空间学习记忆力;TUNEL法检测海马部位神经元的凋亡情况;Western blot法检测脑组织GSK-3β和TNF-α蛋白的表达,并检测凋亡相关通路蛋白p38及caspase-3的表达。结果 与模型组相比,绞股蓝总苷高、中、低剂量组逃避潜伏期显著缩短(P<0.01),穿台次数明显增多(P<0.05);海马部位神经元凋亡数量明显减少(P<0.01);GSK-3β和TNF-α蛋白的表达显著降低(P<0.01);caspase-3和P38的表达显著降低(P<0.01)。结论 绞股蓝总苷通过抑制凋亡通路P38/caspase-3的激活,减少神经元凋亡,从而对神经元发挥保护作用。  相似文献   

9.
目的 探讨注射用益气复脉(冻干)(YQFM)对心力衰竭感染性休克大鼠的药效作用。方法 通过结扎冠状动脉左前降支以及尾静脉推注脂多糖(LPS,25 mg·kg-1)的方法建立心力衰竭感染性休克大鼠模型,随机将造模后大鼠分为模型组,肾上腺素(10 μg·kg-1)组,YQFM低、高剂量(232.2、464.3 mg·kg-1)组,联合给药(肾上腺素10 μg·kg-1+YQFM 464.3 mg·kg-1)组,假手术组进行同样操作但不结扎不推注LPS。造模后即给药,尾iv给药1次,模型组和假手术组大鼠给予等体积的0.9%氯化钠注射液。使用八通道无创血压仪检测造模前、造模后及给药后大鼠收缩压变化;ELISA法检测各组大鼠血清中脑钠肽(BNP)、氨基端前心钠肽(NT-proANP)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和超氧化物歧化酶(SOD)水平。结果 各组大鼠的基础收缩压无显著性差异,与假手术组比较,造模各组大鼠收缩压显著降低(P<0.001);与模型组比较,各给药组大鼠收缩压显著回升(P<0.05、0.001)。与假手术组相比,模型组血清NT-proANP、BNP、CK-MB、LDH、ALT、AST水平显著升高(P<0.001),SOD水平显著降低(P<0.001);与模型组相比,肾上腺素组,YQFM 232.2、464.3 mg·kg-1组和联合给药组的NT-proANP、BNP、CK-MB、LDH、ALT、AST水平均显著下降(P<0.05、0.01、0.001),肾上腺素组、YQFM 464.3 mg·kg-1组和联合给药组SOD水平显著升高(P<0.05、0.01、0.001)。结论 YQFM可以显著回升心力衰竭感染性休克大鼠的收缩压水平,改善血清中相关生化指标水平,并且与肾上腺素联合应用效果最好。  相似文献   

10.
目的 评价雷公藤红素对高脂饮食诱导的代谢相关脂肪性肝病(MAFLD)大鼠的保护作用,并探讨其可能的作用机制。方法 60只健康雄性Wistar大鼠,随机分为6组:对照组、模型组、水飞蓟素胶囊组(阳性对照,100 mg·kg−1)和雷公藤红素低、中、高剂量(125、250、500 μg·kg−1)组,每组10只。对照组给予普通饲料喂养,其余5组给予高脂饲料喂养建立MAFLD模型,造模4周后,从第5周开始给药,ig给予相应剂量的药物至第8周。记录大鼠体质量和肝脏湿质量,计算肝脏系数;腹主动脉取血,检测大鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平;HE染色观察肝脏病理变化;Western blotting法检测肝脏中NOD样受体热蛋白结构域相关蛋白3(NLRP3)和半胱氨酸蛋白酶-1(Caspase-1)蛋白表达水平。结果 与模型组比较,雷公藤红素各剂量组的肝脏病理学表现均有所改善,肝脏系数均显著降低(P<0.05、0.01);中、高剂量组大鼠血清中TC、TG、LDL-C、AST、ALT、TNF和IL-1β水平均显著降低(P<0.05、0.01);肝脏中NLRP3和Caspase-1的蛋白表达显著减少(P<0.05、0.01)。结论 雷公藤红素可明显减轻MAFLD大鼠的肝脏病理学损伤,改善血脂水平,其机制可能与调控NLRP3通路密切相关。  相似文献   

11.
12.
Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.
Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.
  相似文献   

13.
14.
This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.  相似文献   

15.
16.
Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.  相似文献   

17.
The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.  相似文献   

18.
Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.  相似文献   

19.
In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.  相似文献   

20.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号