猫急性应激诊断标准的完善及其在加巴喷丁片临床试验中的应用

doi:10.11843/j.issn.0366-6964.2025.05.039

摘要/Abstract

摘要：

本研究旨在完善猫急性应激(cat acute stress, CAS)诊断标准，并将该标准应用于临床试验，以评价加巴喷丁片预防CAS的有效性和安全性。使用猫应激评分(cat stress score, CSS)法诊断CAS，在临床收集健康猫和急性应激猫各15只，分别纳入健康组和急性应激组。通过临床资料对比、CSS评估、促肾上腺激素释放激素(corticotropin releasing hormone, CRH)、促肾上腺激素(adrenocorticotropic hormone, ACTH)和肾上腺素(epinephrine, EPI)检测，评价3种激素的诊断价值并完善CAS诊断标准。再使用完善后的CAS诊断标准，在临床收集106只急性应激猫，随机平均分为赋形剂组和加巴喷丁组，共进行3次就诊。第2次就诊前1.5 h，两组试验猫需分别口服推荐剂量的赋形剂片和加巴喷丁片。通过临床资料对比、基础生理指标检查、行为学评估、血常规检查、血生化检查、激素检查和不良反应监测，评价加巴喷丁片预防CAS的有效性和安全性。结果表明，健康组和急性应激组临床资料具备同质性；CRH、ACTH和EPI联合诊断CAS的最佳临界值为0.212，曲线下面积为0.973，灵敏度为100.00%，特异度为86.67%。药物临床试验中，赋形剂组和加巴喷丁组临床资料具备同质性；与赋形剂组相比，加巴喷丁组的CSS差值、体温差值、呼吸频率差值、心率差值、ACTH差值、EPI差值和不良反应发生率(无力、共济失调、嗜睡)显著升高，而整体镇静评分差值显著降低；上述不良反应约发生在用药2~3 h后，持续时间为1.5~3.0 h；加巴喷丁片未导致血常规和血生化指标的改变。综上，本研究建议CAS的诊断标准完善为猫在检测前数小时内受到应激源刺激，检测时血清CRH(pg·mL^-1)、ACTH(pg·mL^-1)和EPI(ng·mL^-1)浓度联合诊断的预测概率值＞0.212，且检测时CSS＞3分。在应激事件前1.5 h以推荐剂量单次口服加巴喷丁片，对CAS有一定预防作用，但可能出现无力、共济失调和嗜睡的不良反应。

关键词: 猫, 急性应激, 应激评分, 加巴喷丁片, 临床试验

Abstract:

The study aims to improve the diagnostic criteria of cat acute stress (CAS). The criteria were then applied to collect cats in the efficacy and safety trial of gabapentin tablets for CAS prevention. CAS was diagnosed by cat stress score (CSS). Fifteen healthy cats and fifteen acute stress cats were collected and divided into the healthy group and the acute stress group, respectively. Through the comparison of clinical data, CSS assessment, and the results of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and epinephrine (EPI) detection, so as to evaluate the diagnostic value for CAS of three kinds of hormone and improve the CAS diagnostic criteria. Then, using the improved diagnostic criteria for CAS in this study, 106 acute stress cats were collected and randomly divided into the placebo group and the gabapentin group. A total of three visits were scheduled, and 1.5 h before the second visit, the cats in the two groups received the recommended dose of placebo tablets and gabapentin tablets orally. The efficacy and safety of gabapentin tablets were evaluated by comparison of clinical data, basic physiological indexes examination, behavioral evaluation, blood routine examination, blood biochemical examination, hormone examination, and adverse reaction monitoring. The results showed that the clinical data of the healthy group and the acute stress group were homogeneous. When CRH, ACTH, and EPI were combined in the diagnosis of CAS, the best critical value was 0.212, the area under the curve was 0.973, the sensitivity was 100.00%, and the specificity was 86.67%. The results of the clinical trial of gabapentin tablets showed that the clinical data of the placebo group and the gabapentin group were homogeneous. Compared with the placebo group, the gabapentin group had significantly higher ΔCSS, Δtemperature, Δrespiratory rate, Δheart rate, ΔACTH, ΔEPI, and incidence of adverse effects (weakness, ataxia, and lethargy), while the Δglobal sedation score was significantly lower. The above adverse reactions occurred about 2-3 h after the drug administration and lasted about 1.5-3.0 h. Gabapentin tablets did not cause changes in blood routine and blood biochemical indicators. In conclusion, this study suggests that the diagnostic criteria of CAS can be improved as follows: when the cat is stimulated by a stressor within a few hours before the test, the predictive probability value of the combination of serum CRH (pg·mL^-1), ACTH (pg·mL^-1) and EPI (ng·mL^-1) concentrations during the test is greater than 0.212 and the CSS score is greater than 3. A single oral administration of gabapentin tablets at the recommended dose 1.5 h before a stressful event has a certain preventive effect on CAS, but adverse reaction such as atony, ataxia and somnolence may occur.

Key words: cat, acute stress, stress score, gabapentin tablets, clinical trials

中图分类号:

S857.11

朱秋祥, 胡雨林, 朱鑫超, 钟永澄, 丁晓晴, 冀锦朝, 王京煜, 贾坤, 张海洋, 李守军. 猫急性应激诊断标准的完善及其在加巴喷丁片临床试验中的应用[J]. 畜牧兽医学报, 2025, 56(5): 2424-2437.

ZHU Qiuxiang, HU Yulin, ZHU Xinchao, ZHONG Yongcheng, DING Xiaoqing, JI Jinzhao, WANG Jingyu, JIA Kun, ZHANG Haiyang, LI Shoujun. Refinement of the Diagnostic Criteria for Acute Stress in Cats and Its Application in Clinical Trials of Gabapentin Tablets[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(5): 2424-2437.

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得分/分 Score (point)	具体表现 Presentation
-3	非常易激动(过度活跃；不断移动；间歇或持续发声；安静环境下活跃)
-2	有点易激动(易激动；站立并可能间歇性移动；有或没有间歇性发声；对环境保持警惕；活动水平随着环境的变化而增加；最初易兴奋，但在安静的环境中稳定下来)
-1	轻微的兴奋[轻微兴奋；坐着或站着；有或没有间歇性发声；活动水平随着环境的变化(如遮盖物的移动)而增加；在安静的环境平静]
0	正常(警觉、反应灵敏；胸骨横卧或坐着或站着；不发声；意识到环境的变化，随之增加或不增加活动水平；容易在安静的环境中保持平静)
1	轻微镇静(安静、警觉、反应灵敏；胸骨横卧或坐着；无发声；对环境的变化导致活动水平增加量最少；在安静环境中立即平静)
2	有点镇静(态度平静；胸骨横卧；不发声；对环境的变化有或无意识；环境变化后，活动水平并无变化；在安静环境中立即平静)
3	非常镇静(迟钝；胸骨或侧卧；无发声；除听觉刺激外，对环境变化无意识且无反应；对遮盖物的移动无反应)

组别 Groups		健康组 The healthy group	急性应激组 The acute stress group	P值 P value
年龄/月Age (month)		27 (24, 36)	24 (19, 27)	0.106
体重/kg Weight		3.6 (2.8, 4.0)	3.1 (2.5, 3.5)	0.233
性别(雄/雌，例)Sex (male/female)		8/7	10/5	0.710
品种/% Breed	英国短毛猫British shorthair	8	7	1.000
	美国短毛猫American shorthair	4	5
	其他品种Others breeds	3	3

组别Groups	CRH/(pg·mL^-1)	ACTH/(pg·mL^-1)	EPI/(ng·mL^-1)
健康组The healthy group	39.93 (37.63, 42.66)	40.75±6.34	10.50±2.24
急性应激组The acute stress group	42.39 (36.15, 59.26)	54.59±13.53^**	9.90±2.45
P值P value	0.389	0.002	0.487

指标Indexes	CRH	ACTH	EPI	联合诊断Combined diagnosis
曲线下面积AUC	0.596	0.836	0.569	0.973
95%置信区间95% CI	0.375~0.816	0.693~0.978	0.359~0.779	0.926~1.000
截断值Cutoff value	48.88 pg·mL^-1	47.54 pg·mL^-1	10.13 ng·mL^-1	0.212
灵敏度/% Sensitivity	46.67	60.00	60.00	100.00
特异度/% Specificity	93.33	93.33	66.67	86.67
约登指数Youden index	0.400	0.533	0.267	0.867
P值P value	0.373	0.002	0.520	＜0.001

组别 Groups		赋形剂组 The vehicle group	加巴喷丁组 The gabapentin group	P值 P value
年龄/月Age (month)		24.0 (22.0, 28.5)	24.0 (19.0, 35.5)	0.992
体重/kg Weight		3.1 (2.5, 3.5)	3.3 (2.8, 3.6)	0.144
性别(雄/雌，例)Sex (male/female)		21/32	29/24	0.120
品种/% Breed	英国短毛猫British shorthair	33 (62.3)	28 (52.8)	0.395
	中华田园猫Domestic cat	9 (17.0)	14 (26.4)
	美国短毛猫American shorthair	5 (9.4)	8 (15.1)
	其他品种Others breeds	6 (11.3)	3 (5.7)