三甲基氯化锡对亚慢性染毒大鼠肾氢钾ATP酶活力及蛋白与基因表达的研究

Objective To study the activity、protein and gene expression of renal HK-ATPase (HKA) in rats subchronicly exposed to trimethyltin chloride (TMT). Methods In subchronic toxic test (14-week), 55 female SD rats (age, 6 weeks) were divided randomly into 5 groups: control, low, medium, high and super high dosage, respectively, which drank water with TMT of 0, 8.20, 32.81, 131.25 and 262.50 μg·kg-1 ·d-1 for 14 weeks.Then serum K+ levels were measured; the activities of H K-ATPase (HKA) in kidneys were detected by the method of determinenate phosphorus content;Western Blot assay and real-time PCR were used to exam the protein and mRNA expression levels of HKA in kidneys, respectively. Results The serum K + level in super-high dosage group was (5.6±0.4) mmol/L, which was significantly lower than that [(6.9±0.3) mmol/L] in control group (P＜0.01).The HKA enzymatic activity of kidneys in low and super high dosage groups was 4.50±1.45 and 4.55±0.72 μmolPi·mg prot-1h-1, respectively, which were significantly lower than that (6.55±0.77 μmol Pi ·mg prot-1h-1) in control group (P＜0.05). Conclusion When rats were exposed subchronicly to TMT, the renal HKA activity could reduce, but the expression levels of HKA protein and mRNA did not decrease.     

2,3,7,8-四氯二苯并二噁英急性染毒对小鼠脑组织中Na+-K+-ATP酶和Ca2+-ATP酶活力的影响

目的 研究2,3,7,8-四氯二苯并二噁英(TCDD)对小鼠脑组织中Na+-K+-ATP酶、Ca2+-ATP酶活力的影响.方法 将48只雌雄各半的昆明种小鼠按性别随机分为高、中、低剂量TCDD染毒组和对照组,每组雌雄各6只,TCDD染毒剂量分别为100、10、1 μg/kg,用腹腔注射的方式一次染毒,48 h后,测定脑组织中Na+-K+-ATP酶、Ca2+-ArrP酶活力.结果 雌性低剂量、中剂量染毒组和雄性高剂量染毒组小鼠脑组织中Na+-K+-ATP酶活力[分别为(17.35±3.07)、(16.13±2.42)、(20.25±2.72)μmolPi·mg pro-1·h-1]明显升高,与对照组[分别为(13.60±1.72)、(15.97±1.90) μmol Pi·mg pro-1·h-1相比,差异均有统计学意义(P<0.05).各染毒组小鼠Ca2+-ATP酶活力有增加的趋势,但与对照组比较,差异无统计学意义(P>0.05).结论 TCDD急性染毒能提高小鼠脑组织中Na+-K+-ATP酶的活力,且存在性别差异.     

舍曲林治疗儿童情绪障碍的临床观察

目的 了解舍曲林在儿童情绪障碍治疗中的有效性、安全性、起效时间及有效剂量.方法 对147例应用舍曲林治疗的儿童情绪障碍患儿进行回顾性分析,项目包括有效率、舍曲林用量、起效时间及不良反应.结果 137例患儿遵医嘱定期复诊.治疗后2个月,有效率为80.3%(110/137),不良反应发生率为5.8%(8/137).舍曲林有效剂量为(47.9±19.0)mg/d,起效时间为(20.4±13.2)d;儿童强迫症舍曲林有效剂量[(58.7±26.2)mg/d)]显著高于抑郁障碍[(43.6±14.0)mg/d]、广泛性焦虑障碍[(44.4±10.6)mg/d]及恐怖性焦虑障碍[(43.5±15.5)mg/d](P值均<0.01);抑郁障碍起效时间[(14.0±6.1)d]较儿童强迫症[(26.6±16.3)d]、广泛性焦虑障碍[(22.3±13.9)d]和恐怖性焦虑障碍[(21.4±12.8)d]短(P值均<0.01).结论 舍曲林是治疗儿童情绪障碍的有效药物,起效时间在2～3周,不良反应轻,多数患儿能耐受.对抑郁障碍起效较快,对儿童强迫症有效剂量较大.

Abstract：

Objective To explore the efficacy, safety,time of drug taking effect and therapeutic dosage of sertraline in treatment of child emotional disorder. Method One hundred and forty-seven patientswith child emotional disorder were treated by sertraline and the efficacy rate, therapeutic dosage, the time of drug taking effect and adverse reaction was analyzed retrospectively. Results One hundred and thirty-seven patients were regular visited under supervision of a physician. Two months after treatment, the efficacy rate was 80.3%(110/137) and the rate of adverse reaction was 5.8%(8/137). The therapeutic dosage of sertraline was (47.9 + 19.0) mg/d. The time of drug taking effect was (20.4±13.2) d. The therapeutic dosage of sertraline in obsessive-compulsive disorder [(58.7±26.2) mg/d] was significantly higher than that in depression[(43.6±14.0) mg/d],anxiety disorder[(44.4±10.6) mg/d] and phobia[(43.5±15.5) mg/d](P < 0.01 ). The time of drug taking effect in depression[( 14.0±6.1 ) d] was significantly shorter than that in obsessive-compulsive disorder[(26.6±16.3) d,anxiety disorder [(22.3±13.9) d] and phobia [(21.4±12.8) d] (P <0.01). Conclusions Sertraline is an efficient and safe medicine in treatment of child emotional disorder. Its adverse reaction is slight and most patients can tolerate. But it takes higher therapeutic dosage in obsessive-compulsive disorder and the time of drug taking effect is earlier in depression than in other disorder.     

Analysis of relative factors and prediction model for optimal ovarian response in patients with follicular phase long-acting long protocol北大核心CSCD

Objective To explore the relative factors for best ovarian response in patients undergoing assisted reproductive technology with follicular phase long-acting long protocol, and to establish a Nomogram prediction model of ovarian response. Methods This retrospective cohort study analyzed the clinical data of 1289 patients who received assisted reproductive treatment in the Center for Reproductive Medicine of Fujian Maternity and Child Health Hospital from July 1, 2018 to July 30, 2019. According to the number of oocytes retrieved, there were 164 cases in the low ovarian response group (≤5 oocytes retrieved), 891 cases in the normal ovarian response group (the number of retrieved oocytes was >5, and ≤18), and 234 cases in the high ovarian response group (>18 oocytes retrieved). Independent factors affecting ovarian reactivity were screened by logistic regression, which were the model entry variables, and a Nomogram prediction model was established based on the regression coefficients in the model. Results There were statistically significant differences in age, anti-Müllerian hormone (AMH) level and antral follicle count (AFC) among the three groups [32.43±3.99, 31.48±3.89, 29.91±3.73; (2.53±1.90) μg/L, (3.79±2.20) μg/L, (5.94±3.12) μg/L; 10.24±3.10, 14.50±3.29, 19.81±3.44; all P<0.001]. There were no significant differences in body mass index (BMI), duration of infertility and causes of tubal infertility (all P> 0.05). The initial dosage of gonadotropin (Gn) used for ovarian hyperstimulation among the three groups was statistically different [(182.62±53.96) U, (166.79±48.20) U, (159.13±43.92) U, P<0.001], while the duration of Gn used and clinical pregnancy rate had no significant differences (all P>0.05). Multifactorial stepwise aggression analysis showed that female age [0.93(0.90-0.96), P=0.007], AFC [1.07(1.03-1.09), P=0.001], AMH [1.29(1.20-1.39), P=0.001], basal follicle-stimulating hormone [0.79(0.73-0.86), P=0.001], luteinizing hormone value [1.11(1.06-1.23), P=0.010], initial dosage of Gn used [1.00(1.00-1.01), P=0.003], total dosage of Gn usd [1.00(0.99-1.00), P=0.001] and the presence or absence of diagnosis of endometriosis [0.63(0.47-0.86), P=0.001] and polycystic ovary syndrome [0.30(0.22-0.91), P=0.030] were independent factors for the occurrence of different ovarian responses during ovarian hyperstimulation. The prediction model of ovarian reactivity was constructed based on the above factors, and the accuracy of predicting the optimal ovarian response state was 95%. The above model was verified with 306 patients' data from August 1, 2019 to October 30, 2019 in this center, and the predicted ovarian response (number of oocytes obtained) of a total of 279 patients was consistent with the actual situation, with a coincidence degree of 91.2%. The consistency index of the model was 0.71. Conclusion We screened out the relevant factors affecting ovarian response in patients undergoing assisted reproductive technology with follicular phase long-acting long protocol, and established a Nomogram prediction model of ovarian response, which could effectively, intuitively and visually predict ovarian reactivity in hyperstimulation. © 2022 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.     

染铅小鼠海马不饱和脂肪酸含量研究

Objective To study possible impairment mechanisms of learning and memory abilities from unsaturated fatty acids in hippocampus of mice exposed to lead.Methods Forty-eight healthy mice were divided into 4 groups:low dose(0.625 g/L),middle dose(1.250 g/L) and high dose(2.500 g/L) of lead solution in diet and control group (distilled water).The mice in treatment groups were fed with lead solution every day while the mice in control group were fed with distilled water for 50 days.After learning and memory abilities were measured,the mice were killed and contents of oleic acid (C 18:1),linoleic acid (C 18:2),linolenic acid (C18:3),arachidonic acid (AA,C20:4),eicosapentaenoic acid (EPA,C20:5) and docosabexaenoie acid (DHA,C22:6) in hippocampus of mice were determined by high performance liquid chromatography (HPLC).Results (1) In the four training days,the mice treated with lead in the middle dose group and high dose group significantly increased the escape latencies compared with the mice treated with distilled water (P＜0.05) ,and on the 4th day,the low dosage mice' s escape latencies were delayed (P＜O.05).The escape latencies of the I st,2nd,3rd and 4th day had significantly positive linear relation with lead dose.Their relative coefficient in turn is r=0.973,0.985,0.929 and 0.936,indicating that lead harmed spatial memory of mice in Morris water maze (MWM).(2)The contents of C18:2 and AA were obviously enhanced in hippocampus of middle and high dosage (P＜0.05);while there was evident decrease in the contents of C 18:3,EPA and DHA (P＜0.05);the content of C 18:1 was decreased significantly in high dosage group (P＜0.01).The mice's escape latencies had significantly negative linear relation with contents of C 18:1,C 18:3,EPA and DHA,while there was positive linear relation significantly with contents of C18:2 and AA.Their relative coefficient in turn was r=-0.901,-0.914,-0.893,-0.855,0.936,0.727.Conclusion Lead interferes with the metabolism of hippocampus fatty acids and affects membrane function in hippocampus of mice,which might contribute to change of the synthesis,metabolism and release of central neurotransmitter and decrease of the learning and memory abilities.     

染铅小鼠海马不饱和脂肪酸含量研究

Objective To study possible impairment mechanisms of learning and memory abilities from unsaturated fatty acids in hippocampus of mice exposed to lead.Methods Forty-eight healthy mice were divided into 4 groups:low dose(0.625 g/L),middle dose(1.250 g/L) and high dose(2.500 g/L) of lead solution in diet and control group (distilled water).The mice in treatment groups were fed with lead solution every day while the mice in control group were fed with distilled water for 50 days.After learning and memory abilities were measured,the mice were killed and contents of oleic acid (C 18:1),linoleic acid (C 18:2),linolenic acid (C18:3),arachidonic acid (AA,C20:4),eicosapentaenoic acid (EPA,C20:5) and docosabexaenoie acid (DHA,C22:6) in hippocampus of mice were determined by high performance liquid chromatography (HPLC).Results (1) In the four training days,the mice treated with lead in the middle dose group and high dose group significantly increased the escape latencies compared with the mice treated with distilled water (P＜0.05) ,and on the 4th day,the low dosage mice' s escape latencies were delayed (P＜O.05).The escape latencies of the I st,2nd,3rd and 4th day had significantly positive linear relation with lead dose.Their relative coefficient in turn is r=0.973,0.985,0.929 and 0.936,indicating that lead harmed spatial memory of mice in Morris water maze (MWM).(2)The contents of C18:2 and AA were obviously enhanced in hippocampus of middle and high dosage (P＜0.05);while there was evident decrease in the contents of C 18:3,EPA and DHA (P＜0.05);the content of C 18:1 was decreased significantly in high dosage group (P＜0.01).The mice's escape latencies had significantly negative linear relation with contents of C 18:1,C 18:3,EPA and DHA,while there was positive linear relation significantly with contents of C18:2 and AA.Their relative coefficient in turn was r=-0.901,-0.914,-0.893,-0.855,0.936,0.727.Conclusion Lead interferes with the metabolism of hippocampus fatty acids and affects membrane function in hippocampus of mice,which might contribute to change of the synthesis,metabolism and release of central neurotransmitter and decrease of the learning and memory abilities.     

染铅小鼠海马不饱和脂肪酸含量研究

Objective To study possible impairment mechanisms of learning and memory abilities from unsaturated fatty acids in hippocampus of mice exposed to lead.Methods Forty-eight healthy mice were divided into 4 groups:low dose(0.625 g/L),middle dose(1.250 g/L) and high dose(2.500 g/L) of lead solution in diet and control group (distilled water).The mice in treatment groups were fed with lead solution every day while the mice in control group were fed with distilled water for 50 days.After learning and memory abilities were measured,the mice were killed and contents of oleic acid (C 18:1),linoleic acid (C 18:2),linolenic acid (C18:3),arachidonic acid (AA,C20:4),eicosapentaenoic acid (EPA,C20:5) and docosabexaenoie acid (DHA,C22:6) in hippocampus of mice were determined by high performance liquid chromatography (HPLC).Results (1) In the four training days,the mice treated with lead in the middle dose group and high dose group significantly increased the escape latencies compared with the mice treated with distilled water (P＜0.05) ,and on the 4th day,the low dosage mice' s escape latencies were delayed (P＜O.05).The escape latencies of the I st,2nd,3rd and 4th day had significantly positive linear relation with lead dose.Their relative coefficient in turn is r=0.973,0.985,0.929 and 0.936,indicating that lead harmed spatial memory of mice in Morris water maze (MWM).(2)The contents of C18:2 and AA were obviously enhanced in hippocampus of middle and high dosage (P＜0.05);while there was evident decrease in the contents of C 18:3,EPA and DHA (P＜0.05);the content of C 18:1 was decreased significantly in high dosage group (P＜0.01).The mice's escape latencies had significantly negative linear relation with contents of C 18:1,C 18:3,EPA and DHA,while there was positive linear relation significantly with contents of C18:2 and AA.Their relative coefficient in turn was r=-0.901,-0.914,-0.893,-0.855,0.936,0.727.Conclusion Lead interferes with the metabolism of hippocampus fatty acids and affects membrane function in hippocampus of mice,which might contribute to change of the synthesis,metabolism and release of central neurotransmitter and decrease of the learning and memory abilities.     

染铅小鼠海马不饱和脂肪酸含量研究

Objective To study possible impairment mechanisms of learning and memory abilities from unsaturated fatty acids in hippocampus of mice exposed to lead.Methods Forty-eight healthy mice were divided into 4 groups:low dose(0.625 g/L),middle dose(1.250 g/L) and high dose(2.500 g/L) of lead solution in diet and control group (distilled water).The mice in treatment groups were fed with lead solution every day while the mice in control group were fed with distilled water for 50 days.After learning and memory abilities were measured,the mice were killed and contents of oleic acid (C 18:1),linoleic acid (C 18:2),linolenic acid (C18:3),arachidonic acid (AA,C20:4),eicosapentaenoic acid (EPA,C20:5) and docosabexaenoie acid (DHA,C22:6) in hippocampus of mice were determined by high performance liquid chromatography (HPLC).Results (1) In the four training days,the mice treated with lead in the middle dose group and high dose group significantly increased the escape latencies compared with the mice treated with distilled water (P＜0.05) ,and on the 4th day,the low dosage mice' s escape latencies were delayed (P＜O.05).The escape latencies of the I st,2nd,3rd and 4th day had significantly positive linear relation with lead dose.Their relative coefficient in turn is r=0.973,0.985,0.929 and 0.936,indicating that lead harmed spatial memory of mice in Morris water maze (MWM).(2)The contents of C18:2 and AA were obviously enhanced in hippocampus of middle and high dosage (P＜0.05);while there was evident decrease in the contents of C 18:3,EPA and DHA (P＜0.05);the content of C 18:1 was decreased significantly in high dosage group (P＜0.01).The mice's escape latencies had significantly negative linear relation with contents of C 18:1,C 18:3,EPA and DHA,while there was positive linear relation significantly with contents of C18:2 and AA.Their relative coefficient in turn was r=-0.901,-0.914,-0.893,-0.855,0.936,0.727.Conclusion Lead interferes with the metabolism of hippocampus fatty acids and affects membrane function in hippocampus of mice,which might contribute to change of the synthesis,metabolism and release of central neurotransmitter and decrease of the learning and memory abilities.     

染铅小鼠海马不饱和脂肪酸含量研究

Objective To study possible impairment mechanisms of learning and memory abilities from unsaturated fatty acids in hippocampus of mice exposed to lead.Methods Forty-eight healthy mice were divided into 4 groups:low dose(0.625 g/L),middle dose(1.250 g/L) and high dose(2.500 g/L) of lead solution in diet and control group (distilled water).The mice in treatment groups were fed with lead solution every day while the mice in control group were fed with distilled water for 50 days.After learning and memory abilities were measured,the mice were killed and contents of oleic acid (C 18:1),linoleic acid (C 18:2),linolenic acid (C18:3),arachidonic acid (AA,C20:4),eicosapentaenoic acid (EPA,C20:5) and docosabexaenoie acid (DHA,C22:6) in hippocampus of mice were determined by high performance liquid chromatography (HPLC).Results (1) In the four training days,the mice treated with lead in the middle dose group and high dose group significantly increased the escape latencies compared with the mice treated with distilled water (P＜0.05) ,and on the 4th day,the low dosage mice' s escape latencies were delayed (P＜O.05).The escape latencies of the I st,2nd,3rd and 4th day had significantly positive linear relation with lead dose.Their relative coefficient in turn is r=0.973,0.985,0.929 and 0.936,indicating that lead harmed spatial memory of mice in Morris water maze (MWM).(2)The contents of C18:2 and AA were obviously enhanced in hippocampus of middle and high dosage (P＜0.05);while there was evident decrease in the contents of C 18:3,EPA and DHA (P＜0.05);the content of C 18:1 was decreased significantly in high dosage group (P＜0.01).The mice's escape latencies had significantly negative linear relation with contents of C 18:1,C 18:3,EPA and DHA,while there was positive linear relation significantly with contents of C18:2 and AA.Their relative coefficient in turn was r=-0.901,-0.914,-0.893,-0.855,0.936,0.727.Conclusion Lead interferes with the metabolism of hippocampus fatty acids and affects membrane function in hippocampus of mice,which might contribute to change of the synthesis,metabolism and release of central neurotransmitter and decrease of the learning and memory abilities.     

百草枯对发育中小鼠学习记忆能力的影响

目的 探讨百草枯对发育中小鼠学习记忆能力的影响及可能的氧化损伤机制.方法 80只健康21 日龄断奶未成熟昆明种小鼠随机分为低、中、高剂量百草枯染毒组和对照组(四蒸水),每组20只,百草枯染毒剂量分别为0.89、2.67、8.00mg/kg,经口灌胃(1次/d),连续染毒28 d.采用Morris水迷宫和避暗穿梭实验测定小鼠学习记忆能力,微孔板比色法测定血清和海马组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力及谷胱甘肽过氧化物酶(GSH-Px)活力.结果 Morris水迷宫实验中,各染毒组小鼠逃避潜伏期[(57.98±2.78)、(62.35±3.18)、(85.57±5.10)s]均明显高于对照组[(21.74±1.36)s],差异有统计学意义(P<0.05),并有剂量-反应关系(R=0.8629,P<0.05).避暗穿梭实验中,各染毒组小鼠主动回避潜伏期[(5.56±0.29)、(6.08±0.22)、(8.32±0.38)s]高于对照组[(3.50±0.13)s],差异有统计学意义(P<0.05),并有剂量-反应关系(R=0.9579,P<0.05).中、高剂量染毒组血清中MDA含量[(24.76±1.76)、(31.10±4.57)nmol/ml]明显高于对照组[(16.38±6.26)nmol/ml],差异有统计学意义(P<0.05);各染毒组海马组织中MDA含量[(2.26±0.18)、(2.77±0.20)、(3.37±0.39)nmol/mg Pro]明显高于对照组[(1.93±0.39)nmol/mg Pro],差异有统计学意义(P<0.05);各染毒组小鼠血清和海马组织中SOD及GSH-Px活力均低于对照组,差异有统计学意义(P<0.05).结论 百草枯可诱导的发育中小鼠海马组织氧化损伤,并导致小鼠学习记忆能力减退.

Abstract：

Objective To explore the damages of paraquat to the learning and memory ability of developing mice and explore the possible mechanism involving oxidative stress.Methods Eighty healthy Kunming mice in aged 21 days were divided into 4 groups randomly:a control group (distilled water) and three paraquat treatment groups.The doses of paraquat were 0.89,2.67 and 8mg/kg body weight,respectively.Paraquat was administered orally in doses of 0.1 ml/10 g body weight,respectively,once a day and for 28 consecutive days.The Morris water maze test and the shuttling and avoid dark box test were used to detect the learning and memory abilities of mice.The levels of MDA and the activities of SOD and GSH-PX were detected according to the commercial kits manual using a microplate reader.Results Morris water maze test showed that the escape latency of mice after paraquat treatment (57.98 ±2.78,62.35 ±3.18,85.57 ±5.10) were significantly increase compared with the control (21.74±1.36),respectively (P<0.05).There were good dose-response relationship (R=0.8629,P<0.05).The shuttling and avoid dark box test showed that initiative avoidance latency of mice after paraquat treatment (5.56 ±0.29,6.08 ±0.22,8.32 ±0.38) were significantly increase compared with the control (3.50 ±0.13),respectively (P<0.05).There were good dose-response relationship (R=0.9579,P<0.05 ).The levels of MDA in serum of mice in paraquat treatment groups (2.67 and 8mg/kg) (24.76±1.76,31.10±4.57) and in hippocampus of mice in each paraquat treatment groups were significantly increase compared with the control (serum:16.38±6.26,hippocampus:1.93±0.39) (P<0.05,respectively).The activities of SOD in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum:213.25±6.78,hippocampus:197.36±6.37) (P<0.05,respectively).The activities of GSH-PX in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum:583.47±11.23,hippocampus:412.38±13.16) (P<0.05,respectively).Conclusion Paraquat can induce the oxidative damage in hippocampus,and then influence the learning and memory abilities of developing mice.     

大、小鼠吸收和代谢双酚A的差异

目的 探讨相同剂量双酚A(bisphenol A,BPA)经口染毒后,引起大、小鼠血清BPA浓度差异的机制.方法 无特定病原体(specic pathogen free,SPF)级雄性SD大鼠和ICR小鼠各18只,一次性经口给予300 mg/kg的BPA后,在第0.5、1.0、12.0小时时间点各采集6只大、小鼠血液,用荧光-高效液相色谱法(fluorescence-high performance liquid chromatography,FL-HPLC)检测血清中BPA浓度;大、小鼠各6只采用原位小肠吸收模型循环灌流100 ml 0.1 mmol/L BPA灌流液,用FL-HPLC法分别检测第0.5、1.0、2.0小时时间点灌注液中BPA浓度和灌流后2.0 h血清中的浓度;采用逆转录PCR(RT-PCR)方法检测大、小鼠肝脏尿苷二磷酸葡萄糖醛酸转移酶2B1(UDP-glucuronosyltransferase 2B1,UGT2B1)mRNA的表达水平,并采用FL-HPLC法检测UGT2B1的酶活性;大、小鼠各6只禁食24 h后,一次性经口给予300 ms/kg BPA,收集24 h粪便,用FL-HPLC法检测粪便中BPA含量.结果 300 ms/kg BPA经口染毒后第0.5、1.0、12.0小时时间点小鼠血清中BPA浓度分别为(66.57±14.95)、(51.16±16.06)、(22.73±5.00)μg/ml,大鼠血清中BPA浓度分别为(15.63±5.65)、(18.34±5.02)、(7.65±2.58)μg/ml,各时间点小鼠均高于大鼠,差异有统计学意义(F值分别为50.660,17.957,8.420,P值均＜0.05);0～、0.5～、1.0～2.0 h小鼠小肠各时间段吸收速率分别为(10.20±4.20)、(1.49±0.67)、(1.31±0.55)μg·cm-2·min-1均高于大鼠相应时间段吸收率[(1.87 ± 0.69)、(0.47±0.13)、(0.36 ± 0.08)μg·cm-2·min-1],差异均有统计学意义(F值分别为14.954、8.877、11.536,P值均＜0.05).0.1 mmol/L BPA灌肠2 h后小鼠血清中的BPA浓度为(22.64±4.35)μg/ml,高于大鼠的(4.13±0.83)μg/ml,差异有统计学意义(F=74.643,P=0.000);大鼠肝脏中BPA代谢酶UGT2B1 mRNA的表达水平和酶活性明显高于小鼠;300 mg/kg BPA经口染毒24 h后,大鼠经粪便排出的BPA量为(1.50±0.32)mg/g,高于小鼠的(0.57±0.35)ms/g,差异有统计学意义(F=21.215,P=0.001).结论 大、小鼠经口给予300 mg/kg BPA染毒后,由于小鼠肠吸收BPA的能力高于大鼠,而大鼠代谢及排出BPA能力高于小鼠,引起小鼠血清中BPA的浓度明显高于大鼠.     

二巯丙磺钠对溴苯腈急性中毒小鼠中枢神经毒性作用的干预

目的 研究溴苯腈急性染毒对小鼠大脑皮层中γ-氨基丁酸(GABA)和谷氨酸(Glu)含量等指标的影响及二巯丙磺钠(Na-DMPS)的作用.方法 将30只ICR小鼠(雌雄各半)随机分成对照组和染毒组,每组10只.对照组予体积分数为10%的DMSO溶液(20ml/kg)灌胃;染毒组予溴苯腈(200mg/kg)灌胃染毒;Na-DMPS保护组予溴苯腈(200mg/kg)灌胃染毒后,即刻以Na-DMPS(300mg/kg)腹腔注射.观察6 h后处死,采用反相高效液相色谱法测定各组小鼠大脑皮层中GABA、Glu含量,同时采用紫外分光光度计比色法等方法测定大脑皮层中谷氨酰胺(Gln)含量及谷氨酰胺合成酶(GS)、谷氨酸脱羧酶(GAD)、γ-氨基丁酸转氨酶(GABA-T)的活力.结果 与对照组[GABA为(3.41±0.12)μmol/g、Glu为(14.00±0.16)μmol/g、Gln为(1.25±0.19)μmol/g、GAD为(13.50±0.25)μmol·g-1·h-1、GABA-T为(25.51±0.21)μmol·g-1·h-1、GS为(142.19±1.31)U/mgpro]比较,急性中毒组小鼠大脑皮层GABA[(3.14±0.14)μmol/g]含量降低,Glu[(17.54±0.40)μmol/g]和Gln[(3.35±0.27)μmol/g]含量增高,GAD[(11.93±0.15)μmol·g-1·h-1]、GABA-T[(24.15±0.22)μmol·g-1·h-1]、GS[(140.75±1.01)U/mg pro]活力下降,差异均有统计学意义(P＜0.05);与急性中毒组相比,Na-DMPS组GABA[(3.52±0.30)μmol/g]含量升高,Glu[(14.20±0.32)μmol/g]和Gln[(1.32±0.17)μmol/g]含量降低,GAD[(13.01±0.45)μmol·g-1·h-1]、GABA-T[(25.19±0.26)μmol·g-1·h-1]、GS[(142.35±1.20)U/mgpro]活力增强,差异均有统计学意义(P＜0.05);Na-DMPS保护组与对照组相比,大脑皮层中GABA、Glu、Gln含量,GAD、GABA-T、GS活力,差异均无统计学意义(P＞0.05).结论 溴苯腈中毒所致小鼠中枢神经的毒性作用可能与大脑皮层组织中GABA和Glu含量的变化有关,Na-DMPS能改善溴苯腈中毒小鼠大脑皮层组织中GABA和Glu含量.     

三甲基氯化锡引发低血钾症的机制探讨

目的　探讨三甲基氯化锡(trimethyltinchloride,TMT)引发低血钾症的机制。方法　给SD大鼠腹腔注射TMT,观察血浆钾、钠、氯及红细胞内钾的水平,红细胞膜Na     

川芎嗪对阿霉素肾病肾小管间质损伤影响的实验研究

目的 观察川芎嗪对阿霉素肾病肾小管间质损伤的影响,并探讨其可能的机制.方法 雄性SD大鼠40只,按简单随机法分为假手术组、模型组、川芎嗪组及苯那普利组,采用左侧肾脏切除加尾静脉重复注射阿霉素的方法建立阿霉素肾病模型.检测各组大鼠在阿霉素注射前（0周末）,用药2周末、4周末、6周末24h尿蛋白量;观察用药6周末各组大鼠肾功能指标及光镜下肾脏的病理改变,应用免疫组化方法测定肾小管间质内皮素-1（Endothelin-1 ET-1）的表达.结果 模型组24h尿蛋白量[（30.07±2.12） mg/24 h、（201.83 ±8.63） mg/24 h、（470.70 ±58.79） mg/24 h]（用药2周末、4周末、6周末）、血尿素氮[ （20.20 ±2.65） mmol/L]、肌酐[（86.79 ±2.20） μmol/L]水平、肾小管间质的损伤PAS评分（4.38 ±0.26）及ET-1表达（126.92 ±3.63）均显著高于假手术组[分别为（6.75±2.07） mg/24 h、（8.28±0.71 ）mg/24 h、（25.37±4.30） mg/24 h、（8.93±1.05） mmol/L、（49.00±5.34） μmol/L、1.06±0.19、32.09±3.71;P＜0.01];川芎嗪组24h尿蛋白量[（176.93±9.20）mg/24 h、（270.45 ±60.21）mg/24 h]（4周末、6周末）、血尿素氮[（13.75 ±2.60） mmol/L]、肌酐[ （62.49 ±3.29）μmol/L]水平、肾间质小管的损伤PAS评分（2.78±0.10）及ET-1表达（57.44±4.98）均显著低于模型组（P＜0.01）.结论 川芎嗪对肾间质小管损伤有保护作用,其机制与减少尿蛋白的排泄,抑制ET-1的生成有关,从而减轻肾小管间质的炎症反应及纤维化.     

低分子肝素对脓毒症大鼠腹主动脉内皮细胞蛋白C受体和蛋白酶活化受体1表达的影响

目的观察低分子肝素（LMWH）对脓毒症大鼠腹主动脉内皮细胞（VEC）蛋白C受体（EPCR）和蛋白酶活化受体1（PARl）表达的影响。方法采用组织贴块法培养24只Wister大鼠腹主动脉VEC,1：3传代至第4代,分为对照组（n=6）、脓毒症组（LPS1μg／ml,n=6）、LMWH组（LPS1μg/ml＋LMWH5μg/ml,n=6）。分别在第1、3、5天采用流式细胞术（FCM）检测VEC表面的EPCR和PARl的表达。结果脓毒症组EPCR和PARl的表达各时间点均较对照组有明显下降（P〈0．05或P〈0．01）,以第5天最为明显（26．53±7．21VS39．26±2．62,q=6．45,P〈0．01：53．214±15．10VS86．54±11．34,q=6．94,P〈0．01）。LMWH组EPCR和PARl的表达各时间点均高于脓毒症组（P〈0．05）;与对照组比较,EPCR在第1天仍有明显降低（40．86±1．63VS45．41.1±2．82,q=3．51,P〈0．05）,但第3、5天接近对照组水平（41．20±3．32VS42．83±2．66,P〉0．05;39．23±3．33VS39．26±2．62,P〉0．05）,PARl各时问点与对照组比较差异均无统计学意义（P〉0．05）。结论LMWH能有效改善脓毒症内皮细胞EPCR和PARl表达抑制的状态。     

血液灌流对百草枯急性中毒兔血药浓度及组织病理学的影响

目的 观察百草枯(PQ)急性中毒日本大耳白兔血液灌流后血药浓度及组织病理学改变.方法 16只日本大耳白兔随机分为PQ中毒组(8只)及血液灌流治疗组(8只),两组动物以PQ 50 mg/kg染毒,染毒后45 min左右予血液灌流治疗,两组均在不同处理后0.5、1.0、1.5、2.0、3.0、6.0、12.0、24.0、4...     

甲状腺功能减低孕鼠补充甲状腺素对子代脑组织同源盒基因Nkx2.1mRNA表达的影响

目的 通过对妊娠期甲状腺功能减低(甲低)大鼠补充左旋甲状腺素(L-thyroxine,L-T4),探讨甲状腺素对子代鼠脑组织同源盒基因Nkx2.1mRNA表达影响,探讨该基因的表达与甲状腺素水平之间的关系.方法 Wistar雌性大鼠120只,按体重分层随机分为对照组、甲低非治疗组,甲低孕鼠妊娠早期(妊娠第1～17天)补充L-T4高、中、低剂量组,甲低孕鼠妊娠晚期(妊娠第18天至分娩后第20天)补充L-T4高、中、低剂量组,共8组,每组15只;补充L-T4高、中、低剂量分别为:3.5、2.0、0.5μg/100 g体重.各组均给予低碘饮食,对照组饮用碘浓度为200 μg/L碘酸钾溶液,其余7组饮用去离子水.3个月后各组均与正常雄性大鼠交配,确定受孕后各甲低给药组于不同时期给予补充L-T4.各组分别取孕第17天胎鼠、新生及出生后第20天龄仔鼠前脑组织,实时荧光定量PCR(Real-time PCR)检测Nkx2.1mRNA水平.结果 甲低孕鼠妊娠早期补充L-T4高、中、低剂量组,甲低孕鼠妊娠晚期补充L-T4高、中、低剂量组,甲低非治疗组、对照组大鼠血清TT3分别为(0.85±0.17)、(0.81±0.18)、(0.86±0.21)、(0.85±0.20)、(0.89±0.18)、(0.85±0.20)、(0.86±0.20)、(1.08±0.07)nmol/L(F=4.08,P＜0.01);TT4分别为(0.43±0.16)、(0.39±0.11)、(0.39±0.13)、(0.43±0.17)、(0.51±0.19)、(0.43±0.16)、(0.41±0.15)、(39.43±14.16)nmol/L(F=31.99,P＜0.01);FT3分别为(3.29±0.61)、(3.29±0.61)、(3.24±0.61)、(3.28±0.63)、(3.31±0.59)、(3.28±0.50)、(3.24±0.49)、(4.93±0.46)pmol/L(F=5.79,P＜0.01);FT4分别为(3.38±0.80)、(3.31±0.67)、(3.29±0.73)、(3.27±0.71)、(3.48±0.81)、(3.56±0.66)、(3.29±0.61)、(27.29±4.53)pmol/L(F=26.34,P＜0.01).甲低非治疗组在妊娠第17天胎鼠Nkx2.1mRNA水平(9.15×10-5±9.17 × 10-5)低于对照组胎鼠(65.1×10-5±40.90×10-5)(t=66.224,P＜0.05);甲低非治疗组在新生期仔鼠Nkx2.1mRNA水平(3.16×10-5±0.142×10-5)低于对照组仔鼠(55.6×10-5±51.05×10-5)(t=102.225,P＜0.05);甲低非治疗组在生后第20天仔鼠Nkx2.1mRNA水平(8.09×10-5±8.21×10-5)低于对照组仔鼠(13.9×10-5±7.43×10-5)(t=9.235,P＜0.05).甲低孕鼠妊娠早期补充L-T4中等剂量组在妊娠第17天胎鼠、新生、生后第20天仔鼠脑组织Nkx2.1mRNA表达水平逐渐降低,分别为(57.1×10-5±22.90×10-5)、(30.8×10-5±27.20×10-5)、(17.1×10-5±0.623×10-5)(F=13.394,P＜0.01).甲低孕鼠妊娠早期补充L-T4中等剂量组妊娠第17天胎鼠、新生、生后第20天仔鼠脑组织Nkx2.1mRNA水平接近对照组,差异无统计学意义(t值分别为0.225、0.336、0.345,P值均＞0.05).结论 大鼠脑组织同源盒基因Nkx2.1mRNA的表达与甲状腺素水平存在关联.     

大豆异黄酮对非酒精性脂肪肝大鼠肝脏脂代谢的影响

目的 研究大豆异黄酮对非酒精性脂肪肝(NAFLD)大鼠肝脏脂质、血脂、抗氧化指标及肝脏脂肪代谢相关因子的影响.方法 将36只雄性SD大鼠用随机数字表法按体重分层随机分为正常对照组、NAFLD模型对照组、大豆异黄酮低剂量组(10 mg/kg)及高剂量组(20 mg/kg),每组9只.正常对照组采用D12450B饲料(10%脂肪热能),模型对照组和大豆异黄酮干预组采用D12492饲料(60%脂肪热能),喂养12周后,检测各组大鼠肝脏脂质、血脂和抗氧化指标的变化,Western blotting检测大鼠肝组织中固醇调节原件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(FAS)和过氧化物酶体增殖物激活受体α(PPARα)的蛋白表达.结果 正常对照组、NAFLD模型对照组、大豆异黄酮低剂量组、高剂量组肝脏甘油三酯(TG)分别为(8.11±4.13)、(57.06±16.95)、(31.26±10.48)、(31.38±13.25)mmol/mg蛋白(F=22.569,P＜0.01);肝脏游离脂肪酸(FFA)分别为(0.030±0.007)、(0.042±0.009)、(0.038±0.009)、(0.032±0.005)μmol/mg蛋白(F=4.857,P＜0.01);肝脏超氧化物歧化酶(SOD)活性分别为(502.29±23.71)、(201.83±16.99)、(228.93±21.71)、(238.08±15.96)U/mg蛋白(F=9.555,P＜0.01);肝脏丙二醛(MDA)含量分别为(1.29±0.29)、(2.85±0.73)、(2.07±0.49)、(2.03±0.37)nmol/mg蛋白(F=13.449,P＜0.01);肝脏SREBP-1c蛋白表达分别为0.45±0.16、1.42±0.30、1.02±0.31、0.47±0.27(F=24.515,P＜0.01);FAS蛋白表达分别为0.27±0.08、1.97±0.47、1.35±0.30、0.49±0.12(F=60.361,P＜0.01);PPARα蛋白表达分别为2.03±0.56、0.41±0.17、0.81±0.27、0.66±0.16(F=37.97,P＜0.01).结论大豆异黄酮可能通过抑制SREBP-1 c、激活PPARα的表达来减少肝脏脂质沉积,增加抗氧化能力.

Abstract：

Objective To study the effects of soybean isoflavone on liver lipid,serum lipid,antioxidant index and hepatic lipid metabolism associated factors in nonalcoholic fatty liver rats.Methods Thirty-six male rats(SD)were randomly divided into four groups by weight: normal control group,nonalcoholic fatty liver disease(NAFLD) model control group,low-dose isoflavone treatment group (10 mg/kg)and high-dose isoflavone group(20 mg/kg),9 rats in each group.Normal control rats were fed with D12450B(10% fat energy),model control and isoflavone intervention rats were fed with D12492(60%fat energy).Twelve weeks later,liver lipid,serum lipid and antioxidant index were observed.Liver sterol regulatory element binding protein-1 c(SREBP-1 c),fatty acid synthase(FAS)and Peroxisome proliferators activated receptor alpha(PPAR alpha)were detected by western blotting.Results Liver triglyceride(TG)in normal control group,NAFLD model control group,low-dose isoflavone group and high-dose isoflavone group were(8.11 ± 4.13),(57.06 ± 16.95),(31.26 ± 10.48),(31.38 ± 13.25)mmol/mg protein,respectively(F = 22.569,P ＜0.01); liver free fatty acid(FFA)were(0.030 ± 0.007),(0.042 ± 0.009),(0.038 ± 0.009),(0.032 ± 0.005)μmol/mg protein,respectively(F = 4.857,P ＜0.01); liver superoxide dismutase(SOD)activity were(502.29 ± 23.71),(201.83 ± 16.99),(228.93 ± 21.71),(238.08 ±15.96)U/mg protein,respectively(F = 9.555,P ＜0.01); liver malondialdehyde(MDA)were(1.29 ±0.29),(2.85 ± 0.73),(2.07 ± 0.49),(2.03 ± 0.37)nmol/mg protein,respectively(F = 13.449,P ＜0.01);SREBP-1 c protein expression were 0.45 ± 0.16,1.42 ± 0.30,1.02 ± 0.31,0.47 ± 0.27,respectively (F=24.515,P＜0.01);FAS protein expression were 0.27 ±0.08,1.97 ±0.47,1.35-0.30,0.49 ±0.12,respectively(F = 60.361,P ＜0.01); PPARα protein expression were 2.03 ± 0.56,0.41 ± 0.17,0.81 ±0.27,0.66±0.16,respectively(F=37.97,P＜0.01).Conclusion Soy isoflavone can reduce the hepatic lipid deposition and increase antioxidant capacity,the mechanism may be related to inhibition of SREBP-1c and activation of PPARα expression in liver.     

茶多酚对高蛋氨酸饮食诱导大鼠纤维蛋白溶解功能损伤的影响

目的 研究茶多酚( tea polyphenols,TP)对蛋氨酸诱导大鼠纤维蛋白溶解功能损伤的保护作用。方法 取成年雄性Wistar大鼠50只,按体重分层随机分为对照组、模型组,以及TP低、中和高剂量组。对照组喂饲正常基础饲料,模型组及TP组均喂饲3％高蛋氨酸饲料,同时TP低、中、高剂量组每天经灌胃分别给予50、100和200 mg/kg的TP,灌胃体积均为0.5ml/100 9,对照组和模型组给予等体积蒸馏水。8周后断头处死大鼠,采用免疫组织化学链霉亲和素-生物素-过氧化物酶复合物（strept-avidin-biotin complex,SABC）法测定大鼠主动脉弓组织型纤溶酶原激活物（tissue-type plasminogen activator,t-PA）和纤溶酶原激活物抑制剂-1（type-1 plasminogen activator inhibitor,PAI-1）蛋白表达结果;ELISA法测定血浆中t-PA和PAI-1含量;RT-PCR法测定胸主动脉t-PA和PAI-1 mRNA水平。结果 实验结束后,对照组、模型组及TP低、中、高剂量组主动脉弓中t-PA蛋白表达量分别为133.03±10.14、95.46±11.08、111.97±11.91、130.23±10.80、139.39±9.41 (F= 14.15,P＜0.01),PAI-1蛋白表达量分别为90.91±8.67、166.76±12.18、139.63±12.71、134.66±13.19、109.49±10.82(F=31.44,P＜0.01);血浆中tPA含量分别为(10.69±1.26)、(6.13±0.92)、(8.56±1.19)、(9.69±0.92)、(11.97±1.08) ng/ml(F=41.98,P＜0.01),PAI-1含量分别为(6.31±0.81)、(16.98±1.27)、(11.39±0.82)、(8.46±0.67)、(8.08±0.91) ng/ml(F= 207.74,P＜0.01);t-PA mRNA水平分别为1.12±0.02、0.75±0.14、1.01±0.09、0.95±0.08、1.05±0.13(F=5.77,P＜0.05);PAI-1 mRNA水平分别为1.25±0.11、1.74±0.06、1.23±0.05、1.09±0.14、1.23±0.04(F=23.56,P＜0.01)。结论 TP能够调节t-PA和PAI-1的转录及蛋白水平,维持t-PA和PAI-1的平衡状态,修复高蛋氨酸饮食诱导的大鼠纤维蛋白溶解功能损伤。