地榆皂苷Ⅰ调节RhoA/ROCK信号通路对支原体肺炎幼鼠肺组织炎性损伤的影响

doi:10.11958/20260535

天津医药 ›› 2026, Vol. 54 ›› Issue (8): 808-814.doi: 10.11958/20260535

地榆皂苷Ⅰ调节RhoA/ROCK信号通路对支原体肺炎幼鼠肺组织炎性损伤的影响

梁东阁(), 曹欢, 张婷, 何倩倩, 黄晗, 仝瑞防^△()

河南省儿童医院郑州儿童医院呼吸科一病区（邮编450000）

收稿日期:2026-03-05 修回日期:2026-04-07 出版日期:2026-08-15 发布日期:2026-08-07
通讯作者: △E-mail：271344350@qq.com
作者简介:梁东阁（1989），女，主治医师，主要从事儿童呼吸系统疾病研究。E-mail：Liangg122389@163.com
基金资助:
河南省医学科技攻关计划联合共建项目(LHGJ20250585)

Effects of ziyuglycoside I on inflammatory injury in lung tissue of juvenile mice with mycoplasma pneumoniae via regulating the RhoA/ROCK signaling pathway

LIANG Dongge(), CAO Huan, ZHANG Ting, HE Qianqian, HUANG Han, TONG Ruifang^△()

Ward 1 of Respiratory Department, Henan Children’s Hospital Zhengzhou Children’s Hospital, Zhengzhou 450000, China

Received:2026-03-05 Revised:2026-04-07 Published:2026-08-15 Online:2026-08-07
Contact: △E-mail: 271344350@qq.com

梁东阁, 曹欢, 张婷, 何倩倩, 黄晗, 仝瑞防. 地榆皂苷Ⅰ调节RhoA/ROCK信号通路对支原体肺炎幼鼠肺组织炎性损伤的影响[J]. 天津医药, 2026, 54(8): 808-814.

LIANG Dongge, CAO Huan, ZHANG Ting, HE Qianqian, HUANG Han, TONG Ruifang. Effects of ziyuglycoside I on inflammatory injury in lung tissue of juvenile mice with mycoplasma pneumoniae via regulating the RhoA/ROCK signaling pathway[J]. Tianjin Medical Journal, 2026, 54(8): 808-814.

摘要/Abstract

摘要：

目的探讨地榆皂苷Ⅰ调节Ras同源基因家族成员A（RhoA）/Rho相关卷曲螺旋形成蛋白激酶（ROCK）通路对支原体肺炎（MP）幼鼠肺组织炎性损伤的影响。方法将72只小鼠随机分为对照组、MP组、地榆皂苷Ⅰ小剂量组、地榆皂苷Ⅰ大剂量组、阿奇霉素组、地榆皂苷Ⅰ大剂量+RhoA激活剂（溶血磷脂酸）组，每组12只。除对照组外，其余组均通过连续3 d每日经鼻腔滴注肺炎支原体悬液的方式建模。建模成功后给药处理，1次/d，持续7 d。检测小鼠咳嗽潜伏期、咳嗽次数、二氧化碳分压、动脉血氧分压、肺指数；苏木精-伊红（HE）染色检测肺组织病理；酶联免疫吸附试验（ELISA）检测肺组织C-X-C基序趋化因子配体1（CXCL1）、白细胞介素（IL）-1β、肿瘤坏死因子-α（TNF-α）、IL-10水平；TUNEL染色检测肺组织细胞凋亡；Western blot检测肺组织活化型半胱天冬酶-3（cleaved caspase-3）、P53、RhoA、ROCK1、ROCK2蛋白表达。结果与对照组相比，MP组肺组织肺泡间隔显著增宽、大量炎性细胞弥漫性浸润，咳嗽潜伏期缩短，咳嗽次数增加，二氧化碳分压、肺指数、肺组织CXCL1、IL-1β、TNF-α水平、细胞凋亡率及cleaved caspase-3、P53、RhoA、ROCK1、ROCK2蛋白水平升高，动脉血氧分压、肺组织IL-10水平降低（P<0.05）；与MP组相比，地榆皂苷Ⅰ小剂量组、大剂量组和阿奇霉素组上述指标变化趋势相反，且地榆皂苷Ⅰ大剂量组各指标变化较小剂量组显著（P<0.05），地榆皂苷Ⅰ大剂量组与阿奇霉素组差异无统计学意义（P>0.05）；溶血磷脂酸逆转了大剂量地榆皂苷Ⅰ对MP幼鼠肺组织炎性损伤的改善作用。结论地榆皂苷Ⅰ可有效改善MP幼鼠肺组织炎性损伤，其机制可能与抑制RhoA/ROCK通路激活有关。

关键词: 肺炎, 支原体, 炎症, 细胞凋亡, rho相关激酶类, 地榆皂苷Ⅰ, RhoA/ROCK通路

Abstract:

Objective To investigate the effects of ziyuglycoside Ⅰ on inflammatory injury in lung tissue of juvenile mice with mycoplasma pneumoniae (MP) through regulation of the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. Methods Seventy-two mice were randomly divided into the control group, the MP group, the low-dose ziyuglycoside Ⅰ group, the high-dose ziyuglycoside Ⅰgroup, the azithromycin group and the high-dose ziyuglycoside Ⅰ+ RhoA activator (lysophosphatidic acid) group, with 12 mice in each group. Except for the control group, all other groups were modeled by daily intranasal instillation of MP suspension for three consecutive days. After successful modeling, drug treatments were administered once daily for 7 days. Cough latency, cough frequency, partial pressure of carbon dioxide, arterial partial pressure of oxygen and lung index were detected. Pathology of lung tissue was assessed by HE staining. Levels of C-X-C motif chemokine ligand 1 (CXCL1), interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-10 in lung tissue were measured by ELISA. Apoptosis in lung tissue was detected by TUNEL staining. Protein expression levels of cleaved caspase-3, P53, RhoA, ROCK1 and ROCK2 were determined by Western blot assay. Results Compared with the control group, the alveolar septa in lung tissue of the MP group were significantly widened, a large number of inflammatory cells were diffuse infiltration, the cough latency was shortened, cough frequency was increased, partial pressure of carbon dioxide was increased, and lung index, CXCL1, IL-1β, TNF-α, apoptosis rate, and protein expression of cleaved caspase-3, P53, RhoA, ROCK1 and ROCK2 were increased, while arterial partial pressure of oxygen and IL-10 levels in lung tissue were decreased (P<0.05). Compared with the MP group, the changing trends of the above indicators were opposite in the low-dose ziyuglycoside Ⅰ group, the high-dose ziyuglycoside Ⅰgroup and the azithromycin group. Moreover, the changes of each indicator were more significant in the high-dose ziyuglycoside Ⅰ group than those in the low-dose ziyuglycoside Ⅰgroup (P <0.05). There was no significant difference between the high-dose ziyuglycoside Ⅰ group and the azithromycin group (P > 0.05). Lysophosphatidic acid reversed the ameliorative effect of high-dose ziyuglycoside Ⅰon pulmonary inflammatory injury in MP-infected juvenile mice. Conclusion Ziyuglycoside I can effectively ameliorate inflammatory lung injury in MP of juvenile mice, and its mechanism may be related to the inhibition of RhoA/ROCK pathway activation.

Key words: pneumonia, mycoplasma, inflammation, apoptosis, rho-associated kinases, Ziyuglycoside Ⅰ, RhoA/ROCK pathway

中图分类号:

R563.1

图/表 7

参考文献 24

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组别	咳嗽潜伏期/s	咳嗽次数/次
对照组	88.67±7.04	14.23±0.95
MP组	34.46±2.09^a	53.68±3.18^a
地榆皂苷Ⅰ小剂量组	45.73±4.06^b	44.76±4.09^b
地榆皂苷Ⅰ大剂量组	73.65±5.21^bc	25.66±2.28^bc
阿奇霉素组	74.22±6.08^bc	27.15±3.07^bc
地榆皂苷Ⅰ大剂量+溶血磷脂酸组	61.22±4.05^d	35.26±4.03^d
F	192.200^＊＊	248.200^＊＊

组别	咳嗽潜伏期/s	咳嗽次数/次
对照组	88.67±7.04	14.23±0.95
MP组	34.46±2.09^a	53.68±3.18^a
地榆皂苷Ⅰ小剂量组	45.73±4.06^b	44.76±4.09^b
地榆皂苷Ⅰ大剂量组	73.65±5.21^bc	25.66±2.28^bc
阿奇霉素组	74.22±6.08^bc	27.15±3.07^bc
地榆皂苷Ⅰ大剂量+溶血磷脂酸组	61.22±4.05^d	35.26±4.03^d
F	192.200^＊＊	248.200^＊＊

组别	二氧化碳分压/ mmHg	动脉血氧分压/ mmHg	肺指数/ %
对照组	40.67±3.01	105.23±6.93	0.43±0.05
MP组	98.85±6.12^a	51.67±3.28^a	1.05±0.12^a
地榆皂苷Ⅰ小剂量组	81.73±5.03^b	63.78±5.02^b	0.89±0.09^b
地榆皂苷Ⅰ大剂量组	54.67±3.41^bc	97.64±6.26^bc	0.61±0.07^bc
阿奇霉素组	55.21±3.52^bc	98.22±6.08^bc	0.63±0.08^bc
地榆皂苷Ⅰ大剂量+ 溶血磷脂酸组	68.27±4.51^d	81.61±5.02^d	0.73±0.09^d
F	274.700^＊＊	178.200^＊＊	78.530^＊＊

组别	二氧化碳分压/ mmHg	动脉血氧分压/ mmHg	肺指数/ %
对照组	40.67±3.01	105.23±6.93	0.43±0.05
MP组	98.85±6.12^a	51.67±3.28^a	1.05±0.12^a
地榆皂苷Ⅰ小剂量组	81.73±5.03^b	63.78±5.02^b	0.89±0.09^b
地榆皂苷Ⅰ大剂量组	54.67±3.41^bc	97.64±6.26^bc	0.61±0.07^bc
阿奇霉素组	55.21±3.52^bc	98.22±6.08^bc	0.63±0.08^bc
地榆皂苷Ⅰ大剂量+ 溶血磷脂酸组	68.27±4.51^d	81.61±5.02^d	0.73±0.09^d
F	274.700^＊＊	178.200^＊＊	78.530^＊＊

组别	CXCL1	IL-1β
对照组	20.68±1.57	17.23±1.09
MP组	196.88±14.13^a	145.67±9.02^a
地榆皂苷Ⅰ小剂量组	161.72±10.06^b	118.73±7.15^b
地榆皂苷Ⅰ大剂量组	76.62±5.47^bc	42.69±3.27^bc
阿奇霉素组	71.21±5.09^bc	40.28±3.11^bc
地榆皂苷Ⅰ大剂量+溶血磷脂酸组	131.26±10.55^d	79.67±5.08^d
F	325.500^＊＊	500.800^＊＊
组别	TNF-α	IL-10
对照组	40.47±3.05	97.45±5.17
MP组	234.06±15.12^a	21.22±1.45^a
地榆皂苷Ⅰ小剂量组	200.84±11.07^b	36.19±2.71^b
地榆皂苷Ⅰ大剂量组	98.65±5.04^bc	80.64±5.11^bc
阿奇霉素组	95.77±5.08^bc	81.23±5.09^bc
地榆皂苷Ⅰ大剂量+溶血磷脂酸组	143.74±12.04^d	55.75±3.01^d
F	336.500^＊＊	321.500^＊＊

地榆皂苷Ⅰ调节RhoA/ROCK信号通路对支原体肺炎幼鼠肺组织炎性损伤的影响

Effects of ziyuglycoside I on inflammatory injury in lung tissue of juvenile mice with mycoplasma pneumoniae via regulating the RhoA/ROCK signaling pathway

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参考文献 24

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组别	cleaved caspase-3			P53
对照组	0.69±0.09			0.37±0.05
MP组	2.88±0.26^a			1.76±0.21^a
地榆皂苷Ⅰ小剂量组	2.41±0.24^b			1.43±0.18^b
地榆皂苷Ⅰ大剂量组	1.16±0.22^bc			0.69±0.08^bc
阿奇霉素组	1.19±0.25^bc			0.71±0.09^bc
地榆皂苷Ⅰ大剂量+ 溶血磷脂酸组	1.75±0.18^d			1.23±0.19^d
F	90.280^＊＊			77.030^＊＊
组别		RhoA	ROCK1		ROCK2
对照组		0.87±0.09	0.34±0.06		0.12±0.03
MP组		2.57±0.24^a	1.27±0.13^a		0.88±0.10^a
地榆皂苷Ⅰ小剂量组		2.08±0.21^b	1.01±0.16^b		0.69±0.07^b
地榆皂苷Ⅰ大剂量组		1.26±0.19^bc	0.61±0.08^bc		0.28±0.04^bc
阿奇霉素组		1.28±0.20^bc	0.63±0.08^bc		0.26±0.03^bc
地榆皂苷Ⅰ大剂量+ 溶血磷脂酸组		1.65±0.17^d	0.94±0.10^d		0.45±0.06^d
F		64.450^＊＊	58.640^＊＊		136.900^＊＊

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