颈动脉轻度狭窄患者脑部症状发生与肠道菌群代谢产物和内质网应激产物表达之间的关系

龚楚; 赵伊婷; 汤新乐; 杜敏杰; 张裕祥

doi:10.16766/j.cnki.issn.1674-4152.004379

颈动脉轻度狭窄患者脑部症状发生与肠道菌群代谢产物和内质网应激产物表达之间的关系

doi: 10.16766/j.cnki.issn.1674-4152.004379

1.
新疆医科大学第六附属医院检验科，新疆乌鲁木齐 830002
2.
新疆维吾尔自治区儿童医院北京儿童医院新疆医院检验科，新疆乌鲁木齐 830002

基金项目:

新疆维吾尔自治区卫生健康委员会科研基金项目 WIWY-202401

详细信息

通讯作者:
张裕祥，E-mail：ytmnj8811@163.com

中图分类号: R543.4 R363
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出版历程
- 收稿日期: 2025-09-11
- 网络出版日期: 2026-04-11

Relationship between brain symptoms and the expression of intestinal flora metabolites and endoplasmic reticulum stress products in patients with mild carotid stenosis

1.
Department of Laboratory Medicine, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830002, China

摘要

摘要: 目的探讨颈动脉轻度狭窄患者脑部症状发生与肠道菌群代谢产物和内质网应激产物表达之间的关系，明确肠道菌群代谢产物介导内质网应激途径在动脉粥样硬化发生发展中的作用。方法回顾性分析2021年1月—2023年6月在新疆医科大学第六附属医院接受颈动脉超声检查的87例患者的数据集，采用qRT-PCR分析外周血内质网应激标记物C/EBP同源蛋白(CHOP)mRNA水平。收集患者入院后首次新鲜粪便样本，并通过高效液相色谱法分析样本中短链脂肪酸(SCFAs)水平。结果与无症状组相比，症状组高血压例数、斑块长度、斑块面积、外周血CHOP mRNA表达显著增加(P < 0.05)，肠道菌群代谢产物乙酸、丙酸、丁酸、异戊酸、戊酸水平显著降低(P < 0.05)。CHOP mRNA表达与斑块长度、斑块面积均呈正相关关系(r=0.299、0.221，P＜0.01)，与乙酸、丙酸、丁酸、异戊酸、戊酸水平均呈负相关关系(r=-0.324、-0.285、-0.450、-0.233、-0.332，P＜0.05)。斑块长度与丁酸、异戊酸均呈负相关关系(r=-0.302、-0.313，P＜0.01)。斑块面积与丙酸、丁酸、异戊酸均呈负相关关系(r=-0.230、-0.261、-0.276，P＜0.05)。丁酸的预测能力最高，当截止值为8.8时，其AUC为0.902，灵敏度为77.1%，特异度为84.0%。其次为CHOP mRNA表达，当截止值为0.60时，其AUC为0.811，灵敏度为62.9%，特异度为94.0%。结论粪便乙酸、丙酸、丁酸、异戊酸、戊酸水平降低以及外周血CHOP mRNA表达增加可能与轻度颈动脉狭窄患者出现脑部症状相关，并且这些变化又与颈动脉斑块特征相关。
- 肠道菌群代谢产物 /
- 内质网应激 /
- 粪便 /
- 动脉粥样硬化 /
- 脑部症状
Abstract: Objective To explore the relationship between the occurrence of brain symptoms and the expression of intestinal flora metabolites and endoplasmic reticulum stress products in patients with mild carotid stenosis. Methods This study retrospectively analyzed the data sets of 87 patients who received carotid ultrasound examination in our hospital from January 2021 to June 2023, the mRNA level of the endoplasmic reticulum stress marker C/EBP homologous protein (CHOP) in peripheral blood was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The fresh stool samples were collected for the first time after admission, and the levels of short-chain fatty acids (SCFAs) in the samples were analyzed by high-performance liquid chromatography. Results Plaque length, plaque area, and CHOP mRNA expression in peripheral blood in the symptomatic group increased significantly (P < 0.05), while the levels of intestinal flora metabolites such as acetic acid, propionic acid, butyric acid, isovaleric acid, and valeric acid decreased significantly (P < 0.05). CHOP mRNA expression was positively correlated with plaque length and plaque area (r=0.299 and 0.221, all P < 0.01), and negatively correlated with the levels of acetic acid, propionic acid, butyric acid, isovaleric acid, and valeric acid (r=-0.324, -0.285, -0.450, -0.233, and -0.332, all P < 0.05). The length of plaque was negatively correlated with butyric acid and isovaleric acid (r=-0.302 and -0.313, both P < 0.01). The plaque area was negatively correlated with propionic acid, butyric acid, and isovaleric acid (r=-0.230, -0.261, and -0.276, all P < 0.05). The prediction ability of butyric acid was the highest. When the cutoff value was 8.8, its AUC was 0.902, sensitivity was 77.1%, and specificity was 84.0%. Followed by CHOP mRNA expression, when the cutoff value was 0.60, its AUC was 0.811, sensitivity was 62.9%, and specificity was 94.0%. Conclusion The decrease of fecal acetic acid, propionic acid, butyric acid, isovaleric acid, and valeric acid levels and the increase of CHOP mRNA expression in peripheral blood may be related to the occurrence of brain symptoms, and these changes are related to the characteristics of carotid plaque.
- Metabolites of intestinal flora /
- Endoplasmic reticulum stress /
- Feces /
- Atherosclerosis /
- Brain symptoms

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图 1 外周血CHOP mRNA表达与颈动脉斑块特征及肠道菌群代谢产物的相关性热图

注：^*P＜0.05，^**P＜0.01。

Figure 1. Heatmap showing the correlation between peripheral blood CHOP mRNA expression and plaque characteristics, as well as intestinal microbiota metabolites

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图 2 CHOP mRNA表达、斑块特征、肠道菌群代谢产物预测脑血管事件的ROC曲线

Figure 2. ROC curve of CHOP mRNA expression, plaque characteristics and intestinal flora metabolites for predicting cerebrovascular events

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表 1 2组接受颈动脉超声检查患者临床特征比较

Table 1. Comparison of clinical characteristics between the two groups of patients who underwent carotid artery ultrasound examination

项目	症状组(n=35)	无症状组(n=52)	统计量	P值
年龄(x±s，岁)	69.60±10.42	69.58±10.70	0.010^a	0.992
男性[例(%)]	26(74.3)	39(75.0)	0.006^b	0.940
高血压[例(%)]	28(80.0)	28(53.8)	6.239^b	0.012
糖尿病[例(%)]	19(54.3)	24(46.2)	0.553^b	0.457
吸烟[例(%)]	4(11.4)	6(11.5)	0.000^b	0.987
斑块特征
斑块长度[M(P₂₅, P₇₅)，mm]	9.00(5.50, 12.00)	6.00(4.00, 9.00)	2.632^c	0.008
斑块厚度(x±s，mm)	2.87±1.33	2.53±0.98	1.384^a	0.170
斑块面积(x±s，mm²)	35.24±7.07	18.28±2.04	2.305^a	0.027
cIMT(x±s，mm)	1.21±0.30	1.19±0.32	0.202^a	0.840
DoS(x±s，%)	35.39±11.79	32.28±12.70	1.146^a	0.255
肠道菌群代谢产物
乙酸(x±s，μmol/g)	38.97±14.43	52.46±11.58	4.822^a	＜0.001
丙酸(x±s，μmol/g)	26.97±6.03	31.31±5.18	3.585^a	0.001
丁酸(x±s，μmol/g)	7.49±1.73	11.77±3.54	6.628^a	＜0.001
异戊酸(x±s，μmol/g)	2.71±0.62	3.61±1.04	4.560^a	＜0.001
戊酸(x±s，μmol/g)	2.76±1.15	3.69±1.50	3.083^a	0.003
琥珀酸(x±s，μmol/g)	0.77±0.07	0.79±0.11	0.625^a	0.534
内质网应激指标
CHOP mRNA(x±s)	0.57±0.15	0.40±0.16	4.876^a	＜0.001
注：^a为t值，^b为χ²值，^c为Z值。

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表 2 CHOP mRNA表达、斑块特征、肠道菌群代谢产物预测脑血管事件的价值

Table 2. The value of chop mrna expression, plaque characteristics and intestinal flora metabolites to predict cerebrovascular events

项目	截止值	AUC	95% CI	P值	灵敏度(%)	特异度(%)
斑块面积	21.5 mm²	0.664	0.545~0.783	0.011	62.9	72.0
斑块长度	7.5 mm	0.668	0.549~0.787	0.009	62.9	70.0
CHOP mRNA	0.60	0.811	0.711~0.911	< 0.001	62.9	94.0
乙酸	45.9 μmoL/g	0.765	0.664~0.867	< 0.001	71.4	68.0
丙酸	33.0 μmoL/g	0.697	0.586~0.809	0.002	88.6	46.0
丁酸	8.8 μmoL/g	0.902	0.837~0.967	< 0.001	77.1	84.0
异戊酸	3.3 μmoL/g	0.765	0.665~0.864	< 0.001	85.7	60.0
戊酸	3.4 μmoL/g	0.678	0.564~0.792	0.005	80.0	56.0

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