Study on the effect of Shengyang Yiwei Decoction on the immune function of rats with lung cancer based on PI3K/Akt/NF-κB signal pathway

doi:10.11958/20221626

Abstract

Abstract:

Objective To explore the effect of Shengyang Yiwei Decoction on the immune function of lung cancer rats and its possible mechanism. Methods Twelve of 72 SPF Wistar rats were randomly divided as the control group, and the remaining 60 rats were infused with carcinogenic iodized oil solution into trachea to establish lung cancer models. After modeling, model rats were divided into the model group, the cisplatin group (5 mg/kg), the Shengyang Yiwei Decoction group (14 g/kg), the phosphoinositide 3-kinase (PI3K) activator 740 Y-P group (10 mg/kg) and the Shengyang Yiwei Decoction + 740 Y-P group (Shengyang Yiwei Decoction 14 g/kg + 740 Y-P 10 mg/kg), with 12 animals in per group. After corresponding drug intervention, the proportions of peripheral blood T lymphocyte subsets CD3⁺, CD4⁺ and CD8⁺were detected by flow cytometry, and CD4⁺/CD8⁺ ratio was calculated. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and immunoglobulin (IgG，IgA，IgM) levels. Samples of lung, spleen and thymus were taken and weighed to calculate the indexes of lung, spleen and thymus. HE staining was performed to observe the pathological changes of lung tissue. Real-time fluorescent quantitative PCR (RT-qPCR) was performed to measure the expression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) mRNA in lung tissue. Western blot assay was performed to measure PI3K/protein kinase B (Akt)/nuclear factor-κB (NF-κB) pathway related protein expression in lung tissue. Results Compared with the control group, CD3⁺, CD4⁺ proportions, CD4⁺/CD8⁺ ratio, spleen index and thymus index，IgG，IgA and IgM levels were decreased in the model group, and CD8⁺ proportion, lung index, IL-6 and TNF-α levels, lung tissue ICAM-1 mRNA and MMP-9 mRNA levels, p-PI3K/PI3K, p-Akt/Akt ratios and nuclear NF-κB p65 protein level increased (P<0.05). The left lobe of lung tissue was hyperplasia, squamous epithelial metaplasia and a large number of tumor cells were arranged disorderly in sheets or strips, accompanied by more inflammatory cell infiltration. Compared with the model group, the Shengyang Yiwei Decoction group showed increased CD3⁺ and CD4⁺ proportions, CD4⁺/CD8⁺ ratio, spleen index and thymus index, IgG，IgA，and IgM levels，and decreased CD8⁺ proportion，lung index，IL-6 and TNF-α levels, lung tissue ICAM-1 mRNA and MMP-9 mRNA levels, p-PI3K/PI3K, p-Akt/Akt ratios and nuclear NF-κB p65 protein level (P<0.05). Lung tissue lesions were reduced, lung tissue swelling was not obvious, and the structure of alveolar sacs and epithelial cells were basically clear. On the basis of 740 Y-P, Shengyang Yiwei Decoction could inhibit PI3K/Akt/NF-κB signal pathway and enhance the immunity of lung cancer rats. Conclusion Shengyang Yiwei Decoction may enhance the immune function of T lymphocytes in lung cancer rats by inhibiting PI3K/Akt/NF-κB signaling pathway.

Key words: lung neoplasms, disease models, animal, Shengyang Yiwei Decoction, immunity, phosphoinositol 3-kinase/protein kinase B/nuclear factor- κB signal path

CLC Number:

R734.2，R286.91

Figures/Tables 8

References 27

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组别	CD3⁺/%	CD4⁺/%
对照组	72.64±7.31	65.23±7.12
模型组	48.19±5.24^a	42.18±6.49^a
顺铂组	36.30±4.07^b	30.43±4.80^b
升阳益胃汤组	59.57±7.16^bc	54.90±6.32^bc
740 Y-P组	32.24±4.35^b	27.60±4.28^b
升阳益胃汤+740 Y-P组	45.61±5.29^d	39.08±3.56^d
F	82.799^＊＊	80.689^＊＊
组别	CD8⁺/%	CD4⁺/CD8⁺
对照组	27.34±3.25	2.38±0.17
模型组	38.11±5.16^a	1.10±0.13^a
顺铂组	46.56±5.2^b	0.65±0.10^b
升阳益胃汤组	32.31±6.85^bc	1.68±0.15^bc
740 Y-P组	49.24±5.40^b	0.55±0.09^b
升阳益胃汤+740 Y-P组	40.83±3.62^d	0.96±0.12^d
F	41.064^＊＊	344.714^＊＊

组别	CD3⁺/%	CD4⁺/%
对照组	72.64±7.31	65.23±7.12
模型组	48.19±5.24^a	42.18±6.49^a
顺铂组	36.30±4.07^b	30.43±4.80^b
升阳益胃汤组	59.57±7.16^bc	54.90±6.32^bc
740 Y-P组	32.24±4.35^b	27.60±4.28^b
升阳益胃汤+740 Y-P组	45.61±5.29^d	39.08±3.56^d
F	82.799^＊＊	80.689^＊＊
组别	CD8⁺/%	CD4⁺/CD8⁺
对照组	27.34±3.25	2.38±0.17
模型组	38.11±5.16^a	1.10±0.13^a
顺铂组	46.56±5.2^b	0.65±0.10^b
升阳益胃汤组	32.31±6.85^bc	1.68±0.15^bc
740 Y-P组	49.24±5.40^b	0.55±0.09^b
升阳益胃汤+740 Y-P组	40.83±3.62^d	0.96±0.12^d
F	41.064^＊＊	344.714^＊＊

组别	肺指数	脾指数	胸腺指数
对照组	2.75±0.34	4.91±0.57	2.56±0.31
模型组	4.83±0.56^a	2.52±0.33^a	2.04±0.27^a
顺铂组	3.50±0.41^b	2.03±0.28^b	1.69±0.22^b
升阳益胃汤组	3.62±0.49^b	3.40±0.36^bc	2.45±0.30^bc
740 Y-P组	5.87±0.62^b	1.81±0.25^b	1.42±0.24^b
升阳益胃汤+740 Y-P组	4.90±0.53^d	2.39±0.30^d	1.81±0.23^d
F	62.721^＊＊	120.021^＊＊	33.981^＊＊

组别	肺指数	脾指数	胸腺指数
对照组	2.75±0.34	4.91±0.57	2.56±0.31
模型组	4.83±0.56^a	2.52±0.33^a	2.04±0.27^a
顺铂组	3.50±0.41^b	2.03±0.28^b	1.69±0.22^b
升阳益胃汤组	3.62±0.49^b	3.40±0.36^bc	2.45±0.30^bc
740 Y-P组	5.87±0.62^b	1.81±0.25^b	1.42±0.24^b
升阳益胃汤+740 Y-P组	4.90±0.53^d	2.39±0.30^d	1.81±0.23^d
F	62.721^＊＊	120.021^＊＊	33.981^＊＊

组别	IL-6	TNF-α
对照组	34.26±6.45	24.45±4.20
模型组	61.47±8.39^a	56.29±7.86^a
顺铂组	50.15±7.62^b	43.31±6.45^b
升阳益胃汤组	39.22±6.18^bc	32.06±5.29^bc
740 Y-P组	93.40±10.34^b	81.52±8.37^b
升阳益胃汤+740 Y-P组	70.83±9.56^d	62.48±7.56^d
F	85.268^＊＊	115.121^＊＊