Esquifino A I, Arce A, Stern J E, Cardinali D P
Departamento de Bioquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Eur J Pharmacol. 1995 Oct 16;285(2):143-9. doi: 10.1016/0014-2999(95)00396-3.
This study was performed: (1) to assess whether the stress produced in rats by daily turpentine oil injections for 5 days, or by restraining the animals for 30 min during 5 days, affected basal and Freund's adjuvant-stimulated submaxillary lymph node ornithine decarboxylase activity, an indicator of cell proliferation; (2) to analyze whether the activity of the immunosuppressive drug cyclosporine on submaxillary lymph node ornithine decarboxylase activation after Freund's adjuvant injection was modified in stressed rats; (3) to examine the mediation of stress effects on submaxillary lymph node ornithine decarboxylase activation by regional sympathetic or parasympathetic nerves. Animals subjected to a unilateral superior cervical ganglionectomy, or to a unilateral chorda tympani section, together with a contralateral sham-operation were employed. After turpentine oil or restraint stress, a significant decrease in submaxillary lymph node ornithine decarboxylase was found. A unilateral sympathetic denervation of submaxillary lymph nodes counteracted in part the inhibitory effect of stress on ornithine decarboxylase activation, as well as augmented the enzyme response in innervated submaxillary lymph nodes. Ornithine decarboxylase activation attained similar values in parasympathetic decentralized or intact submaxillary lymph nodes and the unilateral parasympathetic decentralization did not interfere with the inhibition of enzyme activity found in turpentine oil-stressed rats. Cyclosporine administration (5 or 20 mg/kg) significantly decreased Freund's adjuvant-induced ornithine decarboxylase activity in the submaxillary lymph nodes of control rats, but failed to modify it in turpentine oil-stressed animals. In this latter group, a higher (40 mg/kg) dose of cyclosporine decreased ornithine decarboxylase activity on the innervated side only. A diminished inhibitory response to cyclosporine was found in the parasympathetic decentralized submaxillary lymph nodes of unstressed rats. The results support the view that the immunosuppressive effects of cyclosporine may diminish during stress, in part due to changes in the traffic of neural signals in local sympathetic nerves.
（1）评估连续5天每日给大鼠注射松节油，或连续5天每天约束动物30分钟所产生的应激，是否会影响基础状态以及弗氏佐剂刺激后的颌下淋巴结鸟氨酸脱羧酶活性（一种细胞增殖指标）；（2）分析免疫抑制药物环孢素对弗氏佐剂注射后颌下淋巴结鸟氨酸脱羧酶激活的作用，在应激大鼠中是否会发生改变；（3）研究应激对颌下淋巴结鸟氨酸脱羧酶激活的影响是否通过局部交感神经或副交感神经介导。采用接受单侧颈上神经节切除术或单侧鼓索切断术并伴有对侧假手术的动物。在松节油或约束应激后，发现颌下淋巴结鸟氨酸脱羧酶显著降低。颌下淋巴结的单侧交感神经去支配部分抵消了应激对鸟氨酸脱羧酶激活的抑制作用，同时增强了支配侧颌下淋巴结中该酶的反应。在副交感神经去传入或完整的颌下淋巴结中，鸟氨酸脱羧酶激活达到相似值，且单侧副交感神经去传入并不干扰松节油应激大鼠中发现的酶活性抑制。给予环孢素（5或20mg/kg）可显著降低对照大鼠颌下淋巴结中弗氏佐剂诱导的鸟氨酸脱羧酶活性，但在松节油应激动物中未能改变。在后一组中，更高剂量（40mg/kg）的环孢素仅降低了支配侧的鸟氨酸脱羧酶活性。在未应激大鼠的副交感神经去传入颌下淋巴结中，发现对环孢素的抑制反应减弱。这些结果支持以下观点，即环孢素的免疫抑制作用在应激期间可能会减弱，部分原因是局部交感神经中神经信号传递的变化。
