促肾上腺皮质激素对高脂血症兔模型血脂及肾功能的影响

目的:观察促肾上腺皮质激素(ACTH)对高脂血症模型新西兰兔血脂及肾功能的影响.方法:健康雄性新西兰兔30只,饲以2.5%猪油、1.25%胆固醇、0.75%蛋黄粉持续8周.高脂血症模型建立后将其随机分为ACTH组n=15)和对照组(n=15).ACTH组予ACTH1-24100 μg/(kg·d)皮下注射1周,对照组每天予等量生理盐水皮下注射.分别检测并比较两组高脂饮食前后血脂及肾功能情况.结果:ACTH组兔血清TC、HDL及LDL下降,而TG则上升,其中HDL和TG差异有统计学意义,且血Cr显著降低.结论:ACTH具有一定的降脂及改善肾功能效应.但其机制复杂.仍有待于进一步深入研究.     

ACTH短期治疗肾移植术后高脂血症

目的：观察促肾上腺皮质激素(ACTH)对肾移植受者血脂代谢的影响。方法：将30例肾移植术后高血脂患者随机分为ACTH治疗组(n=15)和对照组(n=15)。对照组不给予任何降脂治疗，治疗组接受连续5d的ACTH治疗(25U／d)．分别检测并比较两组血脂变化。结果：治疗组所有患者经ACTH治疗后均有明显的血脂变化，其中TC、TG、LDL、apoB、LP(a)分别减少了11％～26％不等，HDL胆固醇(HDL-c)和apoA1增加了10％～12％。对照组血脂水平无显著变化。结论：ACTH可显著改善肾移植受者的高脂血症，疗效显著，安全可靠，其长期效果有待于进一步观察。     

自控静脉镇痛联合胸椎旁神经阻滞对胸腔镜下肺叶切除术后疼痛及应激反应的影响

目的 探讨自控静脉镇痛(PCIA)联合胸椎旁神经阻滞(TPVB)对胸腔镜下肺叶切除术后疼痛、应激反应的影响。方法 选取2018年2月至2020年12月榆林市第二医院收治的86例行三孔胸腔镜下肺叶切除术患者作为研究对象,按照随机数余数分组方法分为观察组(n=44,PCIA联合单次TPVB治疗)和对照组(n=42,PCIA治疗)。比较两组患者术后不同时间点疼痛程度、镇静情况、应激反应,以及不良反应发生情况。结果 观察组患者术后1、12、24、48 h视觉模拟评分法评分均明显低于对照组,差异均有统计学意义(P<0.05)。两组患者术后1、12、24、48 h Ramsay评分比较,差异均无统计学意义(P>0.05)。两组患者神经阻滞操作前(T1)皮质醇(Cor)、促肾上腺皮质激素(ACTH)水平比较,差异均无统计学意义(P>0.05);观察组患者手术开始后30 min(T2)、气管拔管后30 min(T3)、术后24 h(T4)时Cor、ACTH水平均明显低于对照组,差异均有统计学意义(P<0.05)。两组患者不良反应总发生率比较,差异无统计学意义(P>0.05...     

海洛因依赖者不同剂量美沙酮治疗前后促肾上腺皮质激素和糖皮质激素水平的变化

目的:观察海洛因依赖者用不同剂量美沙酮治疗前后促肾上腺皮质激素(adrenocorticotropin,ACTH)、糖皮质激素(glucocorticoids,GC)及戒断反应强度的变化。方法:将20例海洛因依赖者按入院次序分为全量美沙酮治疗组(n=10),小剂量美沙酮治疗组(n=10),利用放免法测定各治疗组治疗前后ACTH、皮质醇的浓度,并对各组戒断症状在治疗前、治疗不同时期进行评分。结果:治疗前全量美沙酮治疗组和小剂量美沙酮治疗组的ACTH、皮质醇浓度较高,ACTH浓度分别为(18.2±8.2)和(14.2±9.4)ng/L;皮质醇浓度分别为(34.4±5.3)和(33.9±8.9)ng/L;此时两组戒断评分分值较高,分别为29.83±3.17和27.66±2.87。使用不同剂量美沙酮治疗后第3和第10天,各组ACTH、皮质醇浓度和戒断评分分值较治疗前下降。其中全量美沙酮控制戒断症状作用较小剂量美沙酮治疗组好,在治疗第3天和第10天该组的ACTH、皮质醇浓度分别为(11.5±5.4)和(9.8±2.8)ng/L;(26.7±10.0)和(20.8±6.0)ng/L,较治疗前下降明显(t=2.15～4.98,P<0.05)。结论:海洛因依赖者使用不同剂量美沙酮治疗前后,戒断症状分值及下丘脑-垂体-肾上腺轴激素分泌呈先升后降的双向变化,减轻戒断反应可减轻海洛因依赖者ACTH、皮质醇水平。戒断反应可能作为一种应激源引起海洛因依赖者ACTH、     

甲巯咪唑联合普萘洛尔治疗轻中度甲状腺功能亢进症患者甲状腺功能、血清COR及ACTH水平的变化

目的探讨甲巯咪唑联合普萘洛尔治疗对轻中度甲状腺功能亢进症(甲亢)患者甲状腺功能、血清皮质醇(cortisol, COR)、促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)水平的影响。方法选择我院2017年1月—2018年1月诊治的88例轻中度甲亢,按照随机数字表法分为观察组与对照组,每组各44例。对照组予甲巯咪唑治疗,观察组予甲巯咪唑联合普萘洛尔治疗,均治疗3个月。比较临床疗效,检测治疗前后血清促甲状腺激素(thyroid stimulating hormone, TSH)、游离三碘甲状腺素(free triiodothyronine, FT_3)、游离甲状腺素(free thyroxine, FT_4)、COR、ACTH水平变化,观察治疗前后心率变化,记录不良反应发生情况。结果观察组、对照组治疗总有效率分别为95.45%(42/44)、81.82%(36/44),比较差异有统计学意义(χ~2=4.061,P=0.044)。与对照组比较,观察组治疗后TSH、COR水平升高,FT_3、FT_4、ACTH水平与心率降低,差异有统计学意义(P0.001);与本组治疗前比较,两组治疗后TSH、COR水平明显升高,FT_3、FT_4、ACTH水平与心率显著降低,差异有统计学意义(P0.001)。两组不良反应发生率比较差异无统计学意义(P=1.000)。结论甲巯咪唑联合普萘洛尔治疗轻中度甲亢疗效较好,不良反应少,可明显改善甲状腺功能,提高血清COR水平,降低ACTH水平。     

血清SAA和ACTH表达水平与重症细菌感染性疾病的关系及对患者治疗效果的评估

目的探讨血清淀粉样蛋白A(SAA)和促肾上腺皮质激素(ACTH)表达水平与重症细菌感染性疾病的关系,分析其对患者治疗效果的评估价值。方法选取秦皇岛市第一医院2018年1月至2019年1月重症监护室收治的126例感染性疾病患者,根据微生物培养结果分为细菌感染组(n=74)和非细菌感染组(n=52),另选取同期60例体检健康者为对照组。对比各组血清SAA、ACTH水平及白细胞计数(WBC),观察细菌感染组治疗后各时间段血清SAA、ACTH水平及WBC和序贯器官衰竭估计评分(SOFA)评分变化;ROC曲线分析血清SAA、ACTH水平及WBC对重症细菌感染性疾病的诊断价值。结果细菌感染组血清SAA、ACTH水平及WBC值明显高于非细菌感染组(P<0.001),且感染组血清SAA、ACTH水平及WBC值明显高于对照组(P<0.001);细菌感染组治疗后1 d、7 d、14 d、出院前血清SAA、ACTH水平及WBC和SOFA评分逐渐降低。ROC曲线显示,WBC诊断重症细菌感染性疾病的AUC与SAA、ACTH诊断差异无统计学意义(P>0.05),SAA联合ACTH诊断重症细菌感染...     

地塞米松联合脂多糖诱导股骨头坏死模型的构建

背景:对于研究股骨头坏死的发病机制及治疗方法,建立与股骨头坏死病程相似的动物模型是非常重要的。目的:观察地塞米松联合脂多糖诱导兔股骨头坏死的实验效果。方法:健康雄性新西兰大白兔30只,随机分为模型组(n=20)和对照组(n=10)。模型组经耳缘静脉注射2次10μg/kg的脂多糖,再肌肉注射3次地塞米松25mg/kg,对照组注射同等剂量的生理盐水。结果与结论:4周后,CT扫描显示模型组兔股骨头不同程度的骨密度不均匀。显微CT观察发现,模型组骨体积分数、骨矿物质密度、骨矿物质含量和骨小梁厚度均显著低于对照组,而骨小梁间隙高于对照组(P<0.05)。组织学切片见模型组骨细胞陷窝空疏,脂肪细胞增多,部分血管栓塞,其中存活动物的骨坏死率和骨陷窝空虚率均明显低于对照组。说明地塞米松联合脂多糖可有效建立骨坏死模型。     

左旋谷氨酸单钠致大鼠认知障碍的实验观察

目的:观察左旋谷氨酸单钠毁损下丘脑弓状核大鼠的认知功能,探讨其与下丘脑-垂体-肾上腺轴和中枢氨基酸能神经递质与受体的关系。方法:实验于2001-09/2002-03在河南中医学院动物实验中心和中药研究室进行。选取普通级SD大鼠12只,雌雄各半,作为种鼠供实验室繁殖。选取新生鼠23只,随机分为模型组(n=13)和对照组(n=10),分别于出生后第2,4,6,8,10天进行皮下注射左旋谷氨酸单钠4mg/g和生理盐水,每日1次。28d后离乳,再饲养8周后进行跳台试验和Morris水迷宫实验,分别记录各组大鼠的触电潜伏期,错误反应次数及寻台潜伏期,并计算跨台百分率,主要观察各组大鼠的学习记忆行为。实验结束后,全部大鼠用戊巴比妥钠腹腔注射麻醉,心脏取血,采用放免法测定血浆皮质醇、促肾上腺皮质激素。取模型组大鼠8只,对照组大鼠5只,不经灌注固定,冰台上迅速分离大脑,将大脑沿矢状缝分左右半球,左半球用于糖皮质激素受体mRNA原位杂交,右半球采用薄层扫描法测定谷氨酸和γ-氨基丁酸含量,同时取大鼠左侧肾上腺进行苏木精-伊红染色,观察肾上腺组织形态变化。取各组剩余大鼠,用含4%多聚甲醛和0.2%苦味酸的0.1mol/L磷酸盐缓冲液(PB,pH7.4)灌注固定,采用免疫组化法观察海马γ-氨基丁酸受体和N-甲基-D-天门冬氨酸受体1表达,并应用MotaMorph计算机图象分析系统计算免疫反应物质的光密度,取脑组织切片进行Nissl染色。组间比较采用t检验。结果:各组大鼠全部进入结果分析。①跳台实验观察结果:与对照组比较,模型组大鼠测试触电潜伏期显著缩短(t=4.940,P<0.001),训练期和测验期的错误反应次数显著增加(P<0.001～0.01)。②Morris水迷宫实验观察结果:模型组大鼠寻台潜伏期较对照组明显延长(P<0.01),跨台百分率较对照组明显降低(P<0.01)。③下丘脑-垂体-肾上腺-海马轴的观察:模型组大鼠血浆皮质醇及促肾上腺皮质激素水平均较对照组显著升高(t=2.943～4.013,P<0.001～0.01)。模型组海马糖皮质激素受体mRNA表达增强,阳性染色细胞较对照组明显增多。④中枢氨基酸能神经递质与受体的观察:模型组大鼠脑组织谷氨酸含量较对照组显著降低(t=3.063,P<0.05),γ-氨基丁酸含量及谷氨酸/γ-氨基丁酸值较对照组有降低趋势,与对照组比较,模型组海马N-甲基-D-天门冬氨酸受体1及γ-氨基丁酸受体免疫反应物质数密度明显降低(t=2.224～3.682,P<0.01～0.05)。⑤模型组大鼠海马Nissl染色显示模型组细胞稀疏、个数减少、有空泡出现,胞浆着色较浅,细胞轮廓不规整。图像分析模型组大鼠光密度较对照组有降低趋势。结论:模型组大鼠有明显学习记忆障碍,其机制与下丘脑-垂体-肾上腺轴功能亢进,氨基酸能神经递质与受体异常有关。     

哮喘患儿的垂体—肾上腺轴的功能状态：长期吸入二丙酸倍氯米松的影响分析

目的 通过检测相关激素水平，探讨哮喘患儿垂体－肾上腺轴的功能状态及吸入二丙酸倍氯米松对它的影响。方法 将研究对象分成四组：正常对照组、哮喘组、短期吸入（二丙酸倍氯米松）组和长期吸入（二丙酸倍氯米松）组。应用放射免疫法，测定上述四组儿童的促肾上腺皮质激素（ACTH）和皮质醇（Cortisol)水平，以评估垂体－紧上腺轴功能状态。结果 四组儿童的血清ACTH和Cortisol水平之间无明显差异；ACTH刺激后短期吸入治疗组和长期吸入治疗组与正常对照组和哮喘组比较，皮质醇无明显降低。结论 吸入二丙酸倍氯米松治疗一般不会造成下丘脑－垂体－肾上腺轴功能紊乱及抑制肾上腺皮质激素的分泌。     

低剂量雄激素对心肌梗死后心衰成年雄兔血清雄激素水平的影响

目的观察低剂量雄激素十一酸睾酮(TU)和脱氢表雄酮(DHEA)对心肌梗死后心衰雄兔血清雄激素水平的影响。方法对48只4~5月龄健康雄性新西兰大白兔随机行冠状动脉结扎(n=40)或假手术(n=8)。3周后将存活的30只模型兔随机分为3组分别给予TU3mg/kg/2周肌肉注射(TU组,n=10)、DHEA3mg/kg/d口服(DHEA组,n=10)或安慰剂(MI组,n=10)治疗3个月。分别于第0、3、15周观察血清雄激素水平。结果模型兔3周时左室射血分数为(47.6±4.5)%与假手术组的(66.7±5.8)%有显著性差异(P<0.05),应用小剂量TU/DHEA治疗12周后血清游离睾酮升至正常范围,硫酸脱氢表雄酮浓度高于假手术组(P<0.05)。结论本研究中采用的TU和DHEA补充剂量接近心肌梗死后雄兔需要的生理剂量。     

Metabolic consequences of differing protein diets in experimental renal disease

Investigation into the effects of two different dietary proteins, casein and soya, fed at isonitrogenous and isocaloric levels, upon renal function, plasma amino acids and serum lipids, in normal and subtotally nephrectomized rats was undertaken. Groups 1 (24% casein, n = 10) and 2 (24% soya, n = 10) were maintained upon the diets for a 10-week period following subtotal nephrectomy, whilst groups 3 (24% casein, n = 6) and 4 (24% soya, n = 5) served as normal controls. Determination of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and histological analysis were undertaken at the end of the study. Serum lipids and plasma amino acids were determined in subtotally nephrectomized rats (group 5, 24% casein, n = 11: group 6, 24% soya, n = 12) 12 weeks following reduction in renal mass, and serum lipids determined in normal control animals (group 7, 24% casein, n = 10: group 8, 24% soya, n = 10). The glomerular filtration rate and ERPF in normal animals fed casein were significantly greater than those fed soya (P less than 0.01). Survival, proteinuria, renal histological damage and blood urea when killed were all significantly worse in subtotally nephrectomized animals fed casein. Serum cholesterol of groups 5 and 7 fed casein were significantly higher than groups 6 and 8 (P less than 0.05), whilst a significant reduction in serum triglyceride was found for group 6 (P less than 0.001). Plasma amino acids, and essential amino acid ratios of subtotally nephrectomized rats were equivalent, with the exception of plasma glycine (P less than 0.05).     

ACTH and prostaglandin receptors in human adrenocortical tumors. Apparent modification of a specific component of the ACTH-binding site.

The failure of certain adrenal tumors to respond to ACTH was investigated in vivo be administration of corticotropin-(1-24)-tetracosapeptide (ACTH1-24) and dexamethasone and in vitro by studying the binding properties of ACTH1-24 and prostaglandin E1 (PGE1) and their effect on adenylate cyclase activity of the tumors' crude membranes; in addition, in five cases the stimulation of cortisol production in isolated adrenal cells by both hormones and dibuttyryl cyclic adenosine 3',5'-monophosphate (cAMP) was also studied. The results obtained in 13 hormone-producing tumors of the human adrenal cortex, i.e. 10 carcinomas and 3 adenomas, were compared with those found in normal human adrenal glands. According to the adenylate cyclase responses to ACTH1-24 and PGE1, the tumors fall into different categories. In the first group are six rumors in which the adenylate cyclase was stimulated by both ACTH1-24 and PGE; in addition specific binding could be demonstrated for the two hormones in all six. The binding affinity for 125I-ACTH1-24 was found to be about 10 times higher than that for 125I-ACTH11-24. In the one tumor in which the experiment was performed, bound 125I-ACTH1-24 was displaced by ACTH1-10. These results are similar to the ones found in normal human adrenal preparations. For two rumors of the group in which ACTH did not increase steroidogenesis in vivo, the biochemical abnormality might be located beyond cAMP formation. A second group encompasses six tumors in which the steroidogenesis in vivo and the adenylate cyclase activity were insensitive to ACTH1-24 but in which the enzyme was stimulated by PGE1 and NaF. However, these preparations bound 125I-ACTH1-24 and 125I-ACTH11-24, the binding affinity being similar for both peptides but 10 times lower than the one found in normal adrenal cortex for 125I-ACTH1-24. In the only case of this group where it was tested, ACTH1-10 did not displace bound 125I-ACTH1-24. This result strongly suggests the possibility of a modification or a loss of the receptor site that binds the N-terminal sequency (1-10) of ACTH, the biologically active part of the molecule. In the last tumor, both PGE1 and ACTH were unable to stimulate adenylate cyclase activity and steroid production in a preparation of isolated adrenal cells, although steroidogenesis was stimulated by dibutyryl though steroidogenesis was stimulated by dibutyryl cAMP. No specific binding for PGE1 could be demonstrated. However, 125I-ACTH1-24 and 125I-ACTH11-24 were found to be bound to the tumor with the same affinity.     

血清皮质醇和促肾上腺皮质激素水平与肾结石患者输尿管软镜碎石术后早期肾损伤的相关性

目的观察肾结石患者输尿管软镜碎石手术前、后血清皮质醇、促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)水平及术后早期肾损伤发生情况,分析血清皮质醇、ACTH水平与术后早期肾损伤的关系。方法肾结石患者93例,均行输尿管软镜碎石术治疗,根据术后早期(术后48 h内)是否发生肾损伤分为肾损伤组52例和无肾损伤组41例。术前2 h及术后6、12、24、48 h,采用放射免疫法检测患者血清皮质醇、ACTH水平,采用肌氨酸氧化法检测血肌酐水平,并进行2组间比较;采用双变量Pearson直线相关性分析血清皮质醇、ACTH水平与肾结石患者输尿管软镜碎石术后早期肾损伤的相关性;绘制ROC曲线,评估术后12、24 h血清皮质醇、ACTH水平对术后早期肾损伤发生的预测效能。结果 2组术前及术后6、48 h血清皮质醇、ACTH水平比较差异无统计学意义(P>0.05),术后6、12、24、48 h血清皮质醇、ACTH水平均高于术前(P<0.05),肾损伤组术后12、24 h血清皮质醇[(138.54±20.15)、(158.64±22.15)μg/L]、ACTH[(35.68±6.15)、(46.58±7.25)ng/L]水平高于无肾损伤组[(120.64±17.52)、(141.30±18.65)μg/L,(26.35±5.12)、(38.25±6.12)ng/L](P<0.05);2组术前、术后6 h血肌酐水平比较差异无统计学意义(P>0.05),肾损伤组术后12、24、48 h血肌酐水平[(72.25±21.34)、(77.58±25.64)、(98.68±28.64)μmol/L]高于无肾损伤组[(62.02±18.05)、(59.64±20.36)、(55.36±24.16)μmol/L](P<0.05)。术后早期肾损伤患者术后12 h血清皮质醇、ACTH水平与血肌酐呈正相关(r=0.856,P<0.001;r=0.703,P<0.001),血清皮质醇与ACTH水平呈正相关(r=0.752,P<0.001)。术后12 h血清皮质醇、ACTH最佳截断值分别为132.20μg/L、33.30 ng/L时,预测输尿管软镜碎石术后早期肾损伤发生的AUC分别为0.853(95%CI:0.777~0.929,P<0.001)、0.845(95%CI:0.764~0.925,P<0.001);术后24 h血清皮质醇、ACTH最佳截断值分别为148.58μg/L、35.58 ng/L时,预测早期肾损伤发生的AUC分别为0.716(95%CI:0.612~0.819,P<0.001)、0.705(95%CI:0.600~0.811,P<0.001);术后12 h血清皮质醇、ACTH预测术后早期肾损伤发生的AUC(0.853、0.845)及灵敏度(95.82%、91.41%)均高于术后24 h(0.716、0.705,88.67%、82.56%)(P<0.05)。结论肾结石患者输尿管软镜碎石术后血清皮质醇、ACTH均呈高表达,碎石术后动态监测血清皮质醇、ACTH水平变化可预测早期肾损伤的发生风险,术后12 h可作为预测早期肾损伤的有效时点。     

柴胡黄芩不同配伍比例干预急性酒精性肝损伤大鼠肝脾、胸腺、肾上腺指数及肾上腺中维生素C含量的变化

背景:现代医学对酒精性肝损伤的发病机制尚未完全清楚,除了戒酒、支持、对症治疗外,尚无特效的治疗方法。中医药对本病的治疗有着明显的优势,既能改善临床症状又能调理机体免疫功能,有着较好的发展前景。目的:从整体观念出发探讨柴胡、黄芩以不同剂量比例配伍(2∶1,1∶1,1∶2)对大鼠急性酒精性肝损伤的防治作用。设计:完全随机分组设计,空白对照实验。单位:河南中医学院药学院临床中药学实验室。材料:实验于2002-09/11在河南中医学院临床中药学实验室完成。选用健康Wistar大鼠96只,雄性。随机将96只大鼠分为8组:空白组,模型组,柴胡组,黄芩组,小柴胡组,柴胡黄芩2∶1组,柴胡黄芩1∶1组,柴胡黄芩1∶2组,每组12只。方法:①按质量比2∶1,1∶1,1∶2分别称取柴胡、黄芩(480g,240g;360g,360g;240g,480g)制备柴胡水煎液。除空白组(以等体积的生理盐水溶液灌胃)外,其余各组均灌胃给予56度二锅头白酒7mL/kg,2次/d,连续10d造模结束。自造模第1天起,每日灌胃给药2次。空白组和模型组灌服等体积的蒸馏水,其余各组分别灌胃给予相应的药物水煎液,小柴胡组剂量为10g/kg,其余各给药组剂量皆为12g/kg。②末次给酒后16h,腹主动脉取血制备血清。迅速摘取肝脏、脾脏、胸腺、肾上腺。计算脏器指数:脏器指数脏器质量(g)/体质量(g)×100%。计算肾上腺维生素C含量(mg/g):狖[(测定管A值-空白管A值)/(标准管A值-空白管A值)]×标准管浓度(6mg/L)×样品测试前的稀释倍数/组织中蛋白含量(g/L)狚。③组间计量资料比较采用方差齐性检验及单因素方差分析。主要观察指标:各组大鼠肝脏、脾脏、胸腺、肾上腺(右侧)指数及右侧肾上腺中维生素C含量比较。结果:实验过程中模型组大鼠死亡3只,柴胡组、柴胡黄芩1∶1组各死亡2只,其余各组均死亡1只,进入结果分析空白组12只,模型组9只,柴胡组、柴胡黄芩1∶1组各10只,其余各组11只。①各组大鼠肝脏、脾脏、胸腺、肾上腺(右侧)指数的比较:各组大鼠肝脏指数差异不明显。模型组脾脏指数、胸腺指数、肾上腺指数均明显低于空白组(P<0.05～0.01)。柴胡组脾脏指数明显高于模型组,能使降低的脾脏指数趋于正常(P<0.05);黄芩组、柴胡黄芩1:1组、1:2组、小柴胡组胸腺指数明显高于模型组(P<0.05);柴胡黄芩1:2组、小柴胡组肾上腺指数明显高于模型组(P<0.05)。②各组大鼠右侧肾上腺中维生素C含量比较:模型组肾上腺组织中维生素C含量与空白组比较,差异不明显。柴胡组、小柴胡组、柴胡黄芩配伍组肾上腺中维生素C含量均明显低于模型组(P<0.05～0.01),以柴胡黄芩1∶1组的作用趋势最显著(P<0.01)。结论:干预肝脾、胸腺、肾上腺功能损伤可能是柴胡黄芩配伍抗急性酒精性肝损伤的机制之一;各配伍比例中以柴胡黄芩1∶2组作用最明显。     

Cortisol secretion in patients with type 2 diabetes: relationship with chronic complications

OBJECTIVE: The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects. RESEARCH DESIGN AND METHODS: In all subjects, we evaluated ACTH at 8:00 a.m. in basal conditions and serum cortisol levels at 12:00 p.m. (F24) and at 9:00 a.m. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n = 53) or presence (group 2, n = 117) of diabetes complications. RESULTS: In group 2, UFC (125.2 +/- 4.6 nmol/24 h) and F24 (120.6 +/- 4.1 nmol/l) were higher than in group 1 (109.2 +/- 6.8 nmol/24 h, P = 0.057, and 99.7 +/- 6.1 nmol/l, P = 0.005, respectively) and in nondiabetic patients (101.7 +/- 5.9 nmol/24 h, P = 0.002, and 100.3 +/- 5.3 nmol/l, P = 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R = 0.345; P < 0.0001) and diabetes duration (R = 0.39; P < 0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin. CONCLUSIONS: In type 2 diabetic subjects, hypothalamic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications.     

大鼠脑梗死后急性期肾上腺皮质功能改变及地塞米松的干预作用

目的：探讨大鼠脑梗死后急性期肾上腺皮质功能的改变以及地塞米松的干预作用。方法健康雄性SD大鼠60只,随机分为假手术组（对照组）、模型加生理盐水组（安慰剂组）和模型加地塞米松组（治疗组）,每组20只。采用改进的线栓法建立大鼠脑缺血模型。治疗组应用小剂量地塞米松（0.8 mg/kg）替代治疗。各组分别于脑损伤后第3、12、24、72 h 4个时间点进行观察。给予小剂量促肾上腺皮质激素（ACTH）行刺激试验,应用ELISA法测定血清皮质酮（CORT）和ACTH含量。结果安慰剂组大鼠脑损伤后3 h外周血CORT和ACTH均明显高于对照组（P＜0.01）,随后逐渐降低,72 h又有升高趋势;各时间点ACTH刺激后CORT上升值均低于对照组（P＜0.05或P＜0.01）。治疗组伤后所有时间点CORT均高于安慰剂组（P＜0.01或P＜0.05）,ACTH仅24 h高于安慰剂组（P＜0.05）;各时间点ACTH刺激后CORT上升值均高于安慰剂组（P＜0.05或P＜0.01）。结论大鼠脑梗死急性期即存在肾上腺皮质功能不全,随着时间推移,肾上腺储备功能下降,对ACTH反应程度降低。小剂量短疗程肾上腺糖皮质激素可增强肾上腺皮质对ACTH刺激的敏感性。     

Steroidogenesis in the adrenal dysfunction of critical illness: impact of etomidate

ABSTRACT: INTRODUCTION: This study was aimed at characterizing basal and adrenocorticotropic hormone (ACTH)-induced steroidogenesis in sepsis and nonsepsis patients with a suspicion of critical illness-related corticosteroid insufficiency (CIRCI), taking the use of etomidate-inhibiting 11β-hydroxylase into account. METHOD: This was a prospective study in a mixed surgical/medical intensive care unit (ICU) of a university hospital. The patients were 62 critically ill patients with a clinical suspicion of CIRCI. The patients underwent a 250-μg ACTH test (n = 67). ACTH, adrenal steroids, substrates, and precursors (modified tandem mass spectrometry) also were measured. Clinical characteristics including use of etomidate to facilitate intubation (n = 14 within 72 hours of ACTH testing) were recorded. RESULTS: At the time of ACTH testing, patients had septic (n = 43) or nonseptic critical illness (n = 24). Baseline cortisol directly related to sepsis and endogenous ACTH, independent of etomidate use. Etomidate was associated with a lower baseline cortisol and cortisol/11β-deoxycortisol ratio as well as higher 11β-deoxycortisol, reflecting greater 11β-hydroxylase inhibition in nonsepsis than in sepsis. Cortisol increases < 250 mM in exogenous ACTH were associated with relatively low baseline (HDL-) cholesterol, and high endogenous ACTH with low cortisol/ACTH ratio, independent of etomidate. Although cortisol increases with exogenous ACTH, levels were lower in sepsis than in nonsepsis patients, and etomidate was associated with diminished increases in cortisol with exogenous ACTH, so that its use increased, albeit nonsignificantly, low cortisol increases to exogenous ACTH from 38% to 57%, in both conditions. CONCLUSIONS: A single dose of etomidate may attenuate stimulated more than basal cortisol synthesis. However, it may only partly contribute, particularly in the stressed sepsis patient, to the adrenal dysfunction of CIRCI, in addition to substrate deficiency.     

维生素对动脉粥样硬化危险因素损伤血管内皮的保护作用

目的:探讨4种维生素联合应用,对动脉粥样硬化危险因素损伤血管内皮是否具有保护作用。方法:24只雄性家兔被随机分成3组。对照组喂普通饲料,模型组在普通饲料中加入胆固醇、猪油和甲硫氨酸,维生素组饲料同模型组,每天再另外灌胃给予维生素E、C、B6和叶酸,连续8周。第8周末,取血检测相关指标。结果:与对照组相比,模型组血脂(除HDL-C以外)、同型半胱氨酸和内皮素水平均显著升高(t=2.412,P<0.05;t=3.802～5.830,P<0.01),血清一氧化氮虽有降低,但在两组间没有显著差异;HDL-C/LDL-C比值明显减少(t=6.622P<0.01)。与模型组比较,维生素组血清总胆固醇、LDL-C.同型半胱氨酸和血浆内皮素水平均显著降低(t=2.514～2.726,P<0.05),而血清一氧化氮显著升高,HDL-C/LDL-C比值也明显增加(t=4.128～5.076,P<0.01)。结论:维生素E、C、B6和叶酸联合运用,能够降低血中多种危险因子的水平,调节血中内皮素和一氧化氮的平衡,减少或阻断危险因素对内皮功能的损伤,对血管内皮有保护作用。     

Effects of melanotropic peptides on fetal adrenal gland.

Adrenal glands from early, mid, and late fetuses of rabbit, guinea pig, and rat, and from newborn animals of each species, were incubated for 1-4 h with and without 0.1 nM-1 microM ACTH, alpha- or beta-melanocyte-stimulating hormone (alpha MSH or beta MSH). The effects of the peptides were measured on production of glucocorticoids, and on incorporation of labeled thymidine or leucine into DNA or protein, respectively. The findings were similar in all three species. ACTH stimulated synthesis of glucocorticoids throughout fetal life. Potency increased progressively, as reflected by declining minimal effective dose and rising maximal response. In early and mid fetus alpha MSH and beta MSH caused a modest glucocorticoid steroidogenic effect. ACTH and alpha MSH stimulated DNA and protein synthesis in the early and mid fetal gland. alpha MSH was more potent than ACTH in these respects, minimal effective dose being generally 10 times less and maximal response 25-200% greater. The effects diminished or disappeared in the late fetal and newborn gland. These data indicate that alpha- and beta MSH possess steroidogenic or growth-promoting properties, or both, for the fetal adrenal gland.