Mechanism study of BOC2 alleviating SAP inflammatory damage by inhibiting N-formyl peptide/formyl peptide receptor pathway

doi:10.11958/20240774

Abstract

Abstract:

Objective To observe the effect of BOC-Phe-Leu-Phe-Leu-Phe (BOC2) on the expression of six types of mitochondrial N-formyl peptides (NFPs) in blood and two formyl peptide receptors (FPRs) in pancreatic tissue of rats with severe acute pancreatitis (SAP), and to explore its mechanism of alleviating inflammatory damage of SAP. Methods Forty male SD rats were randomly divided into four groups: the sham group, the SAP model group, the BOC2 low-dose and the BOC2 high-dose group (0.1 and 0.2 mg/kg), with 10 animals in each group. The SAP model was prepared by retrograde injection of 5% sodium taurocholate (50 mg/kg) into biliary and pancreatic ducts in the last 3 groups. BOC2 was intraperitoneally injected at 0.5 hours after SAP modeling, and samples were taken 4 hours after modeling. HE staining was used to observe pathological changes in pancreas. Western blot assay was used to detect the expression of NFPs in plasma. IHC staining was used to detect the expression of FPRs in pancreatic tissue. ELISA was used to detect interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α levels in plasma. qPCR was used to detect expression levels of inflammatory factors in local pancreatic tissue. Results Compared with the model group, the BOC2 high-dose group and the BOC2 low- dose group showed improvement in pathological phenomena, such as pancreatic bleeding, acinar cell necrosis, inflammatory cell infiltration and edema. The pancreatic injury score, pancreatic FPRs expression, plasma MT-ND1, MT-ND2, MT-ND3, MT-ND5, MT-ND6 expression, as well as expression levels of three inflammatory factors in plasma and local pancreatic tissue, were significantly reduced (P<0.05). Conclusion BOC2 can reduce the production of inflammatory factors and alleviate SAP inflammatory damage by antagonizing mitochondrial NFPs/FPRs signaling pathway.

Key words: pancreatitis, N-formylmethionine leucyl-phenylalanine, receptors, formyl peptide, mitochondria, BOC2, severe acute pancreatitis

CLC Number:

R576.1

Figures/Tables 10

References 22

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基因	引物序列（5′→3′）	产物大小/bp
IL-1β	上游：GCAGCTTTCGACAGTGAGGA	98
	下游：TCTGGACAGCCCAAGTCAAG	98
IL-6	上游：CACTTCACAAGTCGGAGGCT	114
	下游：TCTGACAGTGCATCATCGCT	114
TNF-α	上游：CTCGAGTGACAAGCCCGTAG	187
	下游：GCAGCCTTGTCCCTTGAAGA	187
GAPDH	上游：GACATGCCGCCTGGAGAAAC	92
	下游：AGCCCAGGATGCCCTTTAGT	92

基因	引物序列（5′→3′）	产物大小/bp
IL-1β	上游：GCAGCTTTCGACAGTGAGGA	98
	下游：TCTGGACAGCCCAAGTCAAG	98
IL-6	上游：CACTTCACAAGTCGGAGGCT	114
	下游：TCTGACAGTGCATCATCGCT	114
TNF-α	上游：CTCGAGTGACAAGCCCGTAG	187
	下游：GCAGCCTTGTCCCTTGAAGA	187
GAPDH	上游：GACATGCCGCCTGGAGAAAC	92
	下游：AGCCCAGGATGCCCTTTAGT	92

组别	腹水量/mL	胰腺干湿质量比/（g/g）
假手术组	0	0.51±0.09
模型组	7.89±0.53^a	0.22±0.05^a
BOC2低剂量组	5.39±0.59^ab	0.36±0.06^ab
BOC2高剂量组	3.80±0.46^abc	0.41±0.06^ab
F	520.973^＊＊	31.964^＊＊

组别	腹水量/mL	胰腺干湿质量比/（g/g）
假手术组	0	0.51±0.09
模型组	7.89±0.53^a	0.22±0.05^a
BOC2低剂量组	5.39±0.59^ab	0.36±0.06^ab
BOC2高剂量组	3.80±0.46^abc	0.41±0.06^ab
F	520.973^＊＊	31.964^＊＊

组别	病理评分/分	CD11b阳性细胞数/（个/视野）
假手术组	0	0
模型组	13.32±0.93^a	90.50±6.35^a
BOC2低剂量组	10.27±0.89^ab	47.60±2.95^ab
BOC2高剂量组	5.98±0.75^abc	22.40±2.72^abc
F	601.452^＊＊	1 068.648^＊＊