目的研究小剂量鱼藤酮长期暴露对大鼠和小鼠中枢多巴胺能神经元的损伤特点。方法昆明小鼠和Wistar大鼠每日腹腔注射鱼藤酮（Rotenone），连续40d。用小鼠攀爬笼检测阿扑吗啡（APO）诱导的定型行为，以HPLC法检测血浆和脑组织鱼藤酮浓度以及脑皮层和纹状体多巴胺（DA）、二羟基苯乙酸（DOPAC）含量。结果注射鱼藤酮20d，大鼠脑皮层和纹状体鱼藤酮明显蓄积，APO诱导的小鼠攀爬行为显著下降，纹状体DA和DOPAC含量也显著降低。鱼藤酮暴露20d和40d，纹状体DA和DOPAC含量均显著下降，且有明显的量效和时效关系。结论重复注射鱼藤酮显著降低动物中枢多巴胺神经递质的含量并导致DA神经行为的异常。

提要：目的探讨急性缺氧条件下4-DMAP对红细胞生成高铁血红蛋白的效应特点。方法新鲜兔血离心洗涤后，置于特制的90% N2+5%O2+5% C02混合气体缺氧罐内孵育，以复制急性缺氧红细胞模型。4-DMAP与缺氧红细胞作用一定时间后，采用分光光度法于波长635nm测定高铁血红蛋白浓度。结果急性缺氧对红细胞的血红蛋白含量无明显影响。当反应体系中4-DMAP浓度为6.49×10-7、6.49×10-6、6.49×10-5、6.49×10-4和6.49×10-3mol/L时，缺氧红细胞生成高铁血红蛋白的能力比常氧红细胞分别提高了22.0%、27.0%、51.44%、3.14%和5.05%。升高反应温度和延长缺氧时间均明显提高4-DMAP药理学效应。结论缺氧增强4-DMAP对红细胞生成高铁血红蛋白的效应。

目的研究化学中毒与急性缺氧两因素的联合效应。方法建立常压常氧、常压缺氧和低压缺氧3种模型,以梭曼（Soman）、氰化钠（NaCN）和42DMAP （4-dimethyl aminophenol）为代表 ,测定大鼠、小鼠、家猫、PC12细胞、兔血红细胞等在3种模型条件下对毒物药物的行为、生化和生理指标变化。结果梭曼单独作用可导致动物协调运动下降、脑等组织含水率增加、脑组织AChE活性降低、MR下调、NE和cAMP含量增加。急性缺氧单独作用也可引起动物协调运动及自主活动的降低、脑等组织含水率的增加、外周血和脑组织AChE活性升高、MR受体上调、NE和cAMP含量增加、42DMAP药效升高。化学中毒与急性缺氧同时作用，上述变化更加复杂。结论化学中毒与急性缺氧两种因素同时作用于机体，对机体产生广泛而复杂的损伤作用。此种作用为两因素的联合效应。缺氧引起的机体功能下降对联合效应的增加部分贡献较大。急性缺氧既可使重要的组织成分发生质或量的变化，也会影响某些抗毒剂的作用强度。

目的探讨硫芥对淋巴细胞的毒性作用方式和分子机制。方法利用硫芥诱导的体外培养淋巴细胞，采用荧光分光光度法检测DNA的损伤，运用逆转录一聚合酶链式反应（RT-PCR）和Western blot方法检测胱氨酸蛋白酶caspase-3的基因和蛋白表达及活化。结果硫芥可导致淋巴细胞DNA损伤，Caspase-3在基因水平和蛋白水平上表达增加，同时发生活化作用，具有时间依赖效应。结论硫芥通过caspase依赖途径诱导淋巴细胞毒作用，Caspase-3的表达与活化参与该过程，影响着淋巴细胞的毒性作用。

目的研究鱼藤酮慢性中毒大鼠尾核脑区及血浆的一氧化氮（ NO）含量和一氧化氮合成酶（NOS）活性的变化规律。方法Wistar大鼠每日皮下注射0.335、0.670、1.005 mg/kg鱼藤酮共90d。于30、60、90d处死动物，分离血浆和尾核脑组织，以生化方法测定NOS活性和NO含量。结果在鱼藤酮中毒30、60、90d3个时相点，大鼠血浆和尾核脑组织中NOS活性和NO含量增加，增加程度因中毒剂量的提高而升高、随中毒时间的延长而升高。结论长期接触鱼藤酮导致血浆和尾核脑组织NOS活性和NO含量升高。

目的探讨硫芥诱导体外培养大鼠脾脏淋巴细胞凋亡及与细胞周期的关系。方法体外分离培养大鼠脾脏淋巴细胞。以流式细胞仪、琼脂糖凝胶电泳分别检测细胞凋亡，细胞周期，和DNA片段改变。结果硫芥可诱导淋巴细胞凋亡（P<0.05），对细胞周期有明显影响，主要是S期和G2/M期明显降低，引起淋巴细胞生长阻滞在G1期；流式细胞仪PI染色出现亚二倍体峰（凋亡峰），其Gl期DNA含量明显增加，S期含量减少；琼脂糖凝胶电泳呈典型的“梯状”带（DNA ladder）。结论硫芥可抑制体外培养的淋巴细胞由Gl期进入S期，抑制体外培养的淋巴细胞增殖，通过诱导淋巴细胞凋亡实现作用机制。

目的探讨caspase-3活性在硫芥诱导淋巴细胞凋亡中的变化和其四肽抑制剂AC-DEVD-CHO对细胞凋亡的干预作用。方法荧光分光光度法检测caspase-3活性变化，琼脂糖凝胶电泳和流式细胞仪分别检测DNA ladder，细胞凋亡率。结果硫芥可诱导淋巴细胞caspase-3活性升高，其多肽抑制剂可部分阻断细胞凋亡，主要表现在抑制剂作用下DNA ladder现象减弱，细胞凋亡百分数下降。结论硫芥通过激活caspase-3诱导淋巴细胞凋亡，其多肽抑制剂对淋巴细胞凋亡具有干预作用。

(-)-Stepholidine (SPD) is an antagonist of normosensitive dopamine (DA) receptors, but it exhibits D1 agonistic action on rotational behaviour in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNC). In the present study, agonistic and antagonistic effects of SPD on the DA receptor-mediated synaptosomal adenylate cyclase (AC) activity in rat striatum were investigated. After blockade of D2 receptors, SPD augmented AC activity dose-dependently. The EC50 value was 41.1±8.6μmol/L. At the concentration of 10 pmol/L, SPD increased CAMP formation from a basal level (50.8±10.3μmol/mg protein/min) to 133.7±31.8μmol/mg protein/min. The SPD-induced stimulation of AC activity was almost completely reversed by 10 μmol/L Sch23390. These results indicate that SPD possesses an agonistic action on the D, receptor. Forskolin-stimulated adenylate cyclase (FSAC) activity was used as a model to elucidate the effect of SPD on D, receptors. The results indicate that DA inhibited FSAC activity dose-dependently, while SPD partially restored FSAC activity. Taken together, these results support the conclusion that SPD has dual actions on DA receptors that mediate AC activity, i.e., an agonistic action on D1 receptors and an antagonistic action on D2 receptors.

(-) Stepholidine (SPD) exhibits antagonist effects on normosensitive dopamine (DA) recep-tors, but it has an agonist action on rotation in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. The present work endeavors to further elucidate the mechanism of its agonist action on D1receptors. [3H] R (+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2, 3, 4, 5-tetrahydro-lH-3-benzazepine ( [3H] SCH-23390) and [3H] spiper-one were used, respectively, as radioligands in D1 and D2 DA receptor binding assays in calf striatal membranes. Experimental data were analyzed by a non-linear regression computer program, GraphPAD InPlot 3.15. The competition curves were fitted first by a single-site equation and then by a two-site equation. The results showed that both apomorphine (APO) and SPD competitively inhibited [3H] SCH-23390 binding. Their competition curves fitted best ro the two-site equation (P<0.05) with a high-affinity site (RH) and a low-affinity site (R) to DA receptors. The K, and K, values (nM) were 2.7±0.45 and 378±62 for APO, and 3.9±2.2 and 126±25 for SPD, respectively. In contrast, the competition curve of SCH-23390, a selective D1DA receptor antagonist, fitted best to a single-site model with a K, value of 1.7±0.5nM. The RH of APO or SPD could be decreased by the addition of 450μM GTP. In the [3H] spiperone binding test, the APO curve was modeled best by the two-site equation, while the SPD curve fitted best to a single-site model. In the rotational behavior test, APO induced 44±20 turns/30 min in the 6-OHDA-lesioned rats, and SPD induced 310±42 turns/30 min, while SCH-23390 antagonized the SPD-induced rotation but did not induce rotational behavior. These results suggest that SPD possesses agonist actions on D1 but antagonist effects on D2 DA receptors. BIOCHEM PHARMACOL 54; 2: 227-232, 1997. 1997 Elsevier Science Inc.

目的研究梭曼中毒PC12细胞中STATs基因mRNA和蛋白表达的变化。方法采用半定量RT-PCR技术和Western blot法检测梭曼中毒2、6、12及24 h的PC12细胞的STAT1、3、5基因mRNA和蛋白质的表达水平，并对PCR产物进行测序。结果梭曼中毒后2h组PC12细胞中STAT1、3、5mRNA和蛋白质表达水平升高，在中毒后12h组达最高，中毒后24h组的表达量低于12h组，与对照组比较均有明显差别。RT-PCR产物直接测序证实扩增产物片断与GenBank中相应序列相同。结论梭曼中毒增强PC12细胞中STATs基因的表达，在梭曼中毒所致的脑损伤中可能发挥重要作用。