Role of SP,CGRP and inflammatory cytokines in the occurences of non erosive esophagitis

doi:10.3877/cma.j.issn.2095-8765.2020.03.005

Abstract

Abstract:

Objective

To explore the mechanism of substance P (SP), calcitonin gene-related peptide (CGRP) and inflammatory cytokines in the development of non erosive reflux disease.

Methods

A total of 25 NERD patients and 10 normal controls were enrolled. All the subjects underwent GERDQ score, 24 h pH monitoring, high resolution esophageal manometry monitoring and endoscopic removal of the local mucosa at 3 cm of the esophageal dentate line as specimens. The expression of SP, CGRP and inflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α) was detected by HE staining and RT-PCR.

Results

24 h esophageal pH monitoring showed that the number of weak acid reflux (4＜pH＜7), acid reflux (pH≤4), acid reflux (%) in proximal esophagus and DeMeester score in NERD group were significantly higher than in control group the t values were -2.365, -2.145, -2.782 and -2.776, and the P values were 0.025, 0.021, 0.021 and 0.017, respectively (P＜0.05). H&E staining showed that there were obvious neutrophil infiltration and pre-inflammatory reaction in esophageal mucosa of NERD group, and the score of inflammation injury was significantly higher than that of control group,the P value were 0.003 (P＜0.01). The relative expression of SP and CGRP in NERD group was significantly higher than that in control group, the P values were 0.0046,0.002, respectively (P＜0.01). In NERD group, the relative expressions of IL-1β, IL-6, IFN-γ and TNF-α in esophageal mucosa were significantly increased,P values were 0.0034, 0.0043, 0.004 and 0.0028, respectively (P＜0.01). Pearson correlation analysis showed that the acid reflux score (DeMeester) in NERD group was positively correlated with the expression of SP, CGRP and inflammatory factors (IL-1β, IL-6, IFN-γ, TNF-α) respectively. The P values 0.003, 0.000, 0.002, 0.005, 0.004 and 0.000, respectively (P＜0.01), the correlation coefficients were r=0.678, 0.686, 0.90, 0.482, 0.374 and 0.415, respectively.

Conclusion

The expression of SP, CGRP and inflammatory cytokines in NERD patients increased significantly, which may be closely related to the increase of esophageal acid sensitivity caused by acid reflux and the occurrence of inflammation.

Key words: non erosive reflux disease, substance p, calcitonin gene-related peptide, inflammatory cytokine

Xiuyun Du, Saimi·Sanmaiti, Xinsheng Zhao, Zanlin Li, Yiliang Li. Role of SP,CGRP and inflammatory cytokines in the occurences of non erosive esophagitis[J]. Chinese Journal of Gastroesophageal Reflux Disease(Electronic Edition), 2020, 07(03): 158-163.

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References 23

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Gene	Forward (5'-3')	Reverse (5'-3')
SP	GCTGTGGGAAAGTGTATGG	GGCAAATTTCTTCTCACCTG
CGRP	CACCAATGTGGGCTCTGAAG	CCGCTTGAGGTTTAGCAGAG
IL-1β	CAGTGAAATGATGGCTTATTAG	CTTTCAACACGCAGGACAGGT
IL-6	GACAGCCACTCACCTCTTCA	CCTCTTTGCTGCTTTCACAC
IFN-γ	TGA ACG CTA CACACT GCA TCT	CGACTCCTT TTCCGCTTCCTGAG
TNF-α	TTGAGGGTTTGCTACAACATGGG	GCTGCACTTTGGAGTGATCG
GAPDH	TGCACCACCAACTGCTTAGC	GGCATGGACTGTGGTCATGAG

Gene	Forward (5'-3')	Reverse (5'-3')
SP	GCTGTGGGAAAGTGTATGG	GGCAAATTTCTTCTCACCTG
CGRP	CACCAATGTGGGCTCTGAAG	CCGCTTGAGGTTTAGCAGAG
IL-1β	CAGTGAAATGATGGCTTATTAG	CTTTCAACACGCAGGACAGGT
IL-6	GACAGCCACTCACCTCTTCA	CCTCTTTGCTGCTTTCACAC
IFN-γ	TGA ACG CTA CACACT GCA TCT	CGACTCCTT TTCCGCTTCCTGAG
TNF-α	TTGAGGGTTTGCTACAACATGGG	GCTGCACTTTGGAGTGATCG
GAPDH	TGCACCACCAACTGCTTAGC	GGCATGGACTGTGGTCATGAG

组别	例数	男性[例数（%）]	年龄（岁）	BMI（kg/m²）
对照组	10	7（70）	29.52±3.53	21.66±1.85
NERD组	25	15（60）	33.65±5.73	22.34±2.36
t值		1.232	2.143	4.895
P值		0.078	0.145	0.426

组别	例数	男性[例数（%）]	年龄（岁）	BMI（kg/m²）
对照组	10	7（70）	29.52±3.53	21.66±1.85
NERD组	25	15（60）	33.65±5.73	22.34±2.36
t值		1.232	2.143	4.895
P值		0.078	0.145	0.426

组别	例数	弱酸反流（次数/次）	酸反流（次数/次）	所有反流总次数/次	食管近端弱酸反流（%）	食管近端酸反流（%）	DeMeester评分
对照组	10	19.67±2.85	15.88±3.41	38.32±1.67	46.63±4.45	38.24±13.78	8.84±3.66
NERD组	25	36.64±6.52	28.13±5.74	42.37±3.25	51.62±7.78	69.74±17.65	19.73±10.35
t值		-2.365	-2.145	5.714	2.651	-2.782	-2.776
P值		0.025	0.021	0.437	0.233	0.021	0.017

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