Study on the mechanism of Fu Fang Ku Shen Zhu She Ye alleviating adverse reactions of 5-fluorouracil chemotherapy in rats with liver cancer

doi:10.11958/20241277

Abstract

Abstract:

Objective To explore effects and action mechanism of Fu Fang Ku Shen Zhu She Ye on adverse reactions of 5-fluorouracil (5-FU) chemotherapy in rats with liver cancer.Methods The rat model of liver cancer was constructed by diethylnitrosamine (DEN). Model rats were divided into the liver cancer group, the chemotherapy group and the chemotherapy +Fu Fang-L/M/H groups. At 24 h after modeling, the chemotherapy group and the chemotherapy + Fu Fang groups were given intraperitoneally injection of 5-FU (100 mg/kg, once/week), and the chemotherapy + Fu Fang-L/M/H groups were given intraperitoneally injection of Fu Fang Ku Shen Zhu She Ye [0.7, 1.4 and 2.8 mL/kg, once/d] for 8 weeks. The cardiac function, myocardial injury markers and pathological changes of myocardial tissue were compared between different groups. Serum levels of brain natriuretic peptide (BNP), cardiac troponin I (cTnI) and creatine kinase MB (CK-MB) were detected by enzyme-linked immunosorbent assay. The expression levels of glucose-regulating protein 78 (GRP78), activating transcription factor 6 (ATF6) and endoplasmic reticulum stress-related protein (CHOP) in myocardial tissue were detected by Western blot assay. Changes of immune function indexes were compared between different groups.Results Compared with the liver cancer group, left ventricular ejection fraction (LVEF) and left ventricular anterior wall thickness in systole (LVAWs) were decreased in the chemotherapy group (P<0.05), left ventricular end diameter in systole (LVEDs), levels of BNP, cTnI and CK-MB were increased (P<0.05), levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in myocardial tissue, expression levels of GRP78, ATF6 and CHOP were increased (P<0.05). Levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺, IgG, IgM and IgA were decreased in the chemotherapy group (P<0.05). The myocardial tissue was disordered, vacuolated and infiltrated by inflammatory cells. Compared with the chemotherapy group, the above indexes and pathological changes of myocardial tissue were significantly improved in the chemotherapy + Fu Fang-L/M/H groups, and the improvement was more significant in the chemotherapy + Fu Fang-H group.Conclusion Fu Fang Ku Shen Zhu She Ye injection can alleviate cardiotoxic injury induced by 5-FU in rats with liver cancer, which may be related to alleviating endoplasmic reticulum stress. It can also alleviate immunosuppression.

Key words: Fu Fang Ku Shen Zhu She Ye, liver cancer, fluorouracil, cardiotoxicity, endoplasmic reticulum stress, immune function

CLC Number:

R285.5

Figures/Tables 7

References 26

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组别	LVEDd/mm		LVAWs/mm		LVAWd/mm
肝癌组	6.15±0.32		1.60±0.19		0.98±0.17
化疗组	6.23±0.40		0.90±0.20^a		1.02±0.20
化疗+复方L组	6.20±0.47		1.00±0.18		1.02±0.23
化疗+复方M组	6.10±0.52		1.45±0.10^bc		1.05±0.27
化疗+复方H组	6.12±0.46		1.48±0.15^bc		1.03±0.23
F	0.098		21.072^＊＊		0.073
组别		LVEF		LVEDs/mm
肝癌组		0.707±0.040		3.20±0.21
化疗组		0.468±0.038^a		4.87±0.31^a
化疗+复方L组		0.535±0.049^b		4.22±0.35^b
化疗+复方M组		0.588±0.036^bc		3.72±0.31^bc
化疗+复方H组		0.652±0.045^bcd		3.28±0.37^bcd
F		30.641^＊＊		29.191^＊＊

组别	LVEDd/mm		LVAWs/mm		LVAWd/mm
肝癌组	6.15±0.32		1.60±0.19		0.98±0.17
化疗组	6.23±0.40		0.90±0.20^a		1.02±0.20
化疗+复方L组	6.20±0.47		1.00±0.18		1.02±0.23
化疗+复方M组	6.10±0.52		1.45±0.10^bc		1.05±0.27
化疗+复方H组	6.12±0.46		1.48±0.15^bc		1.03±0.23
F	0.098		21.072^＊＊		0.073
组别		LVEF		LVEDs/mm
肝癌组		0.707±0.040		3.20±0.21
化疗组		0.468±0.038^a		4.87±0.31^a
化疗+复方L组		0.535±0.049^b		4.22±0.35^b
化疗+复方M组		0.588±0.036^bc		3.72±0.31^bc
化疗+复方H组		0.652±0.045^bcd		3.28±0.37^bcd
F		30.641^＊＊		29.191^＊＊

组别	BNP	cTnI	CK-MB
肝癌组	263.94±10.81	738.36±12.49	982.48±21.11
化疗组	443.68±11.62^a	973.14±15.62^a	1 287.66±34.48^a
化疗+复方L组	410.62±12.41^b	914.08±14.71^b	1 201.39±23.56^b
化疗+复方M组	383.50±13.82^bc	866.32±13.99^bc	1 135.72±28.31^bc
化疗+复方H组	343.83±12.81^bcd	799.87±15.63^bcd	1 058.56±27.44^bcd
F	189.170^＊＊	242.606^＊＊	115.913^＊＊

组别	BNP	cTnI	CK-MB
肝癌组	263.94±10.81	738.36±12.49	982.48±21.11
化疗组	443.68±11.62^a	973.14±15.62^a	1 287.66±34.48^a
化疗+复方L组	410.62±12.41^b	914.08±14.71^b	1 201.39±23.56^b
化疗+复方M组	383.50±13.82^bc	866.32±13.99^bc	1 135.72±28.31^bc
化疗+复方H组	343.83±12.81^bcd	799.87±15.63^bcd	1 058.56±27.44^bcd
F	189.170^＊＊	242.606^＊＊	115.913^＊＊

组别	TNF-α	IL-1β	IL-6
肝癌组	31.84±2.18	2.23±0.18	13.81±1.12
化疗组	58.43±2.29^a	9.12±0.25^a	28.63±2.63^a
化疗+复方L组	52.68±2.41^b	7.51±0.39^b	24.59±1.87^b
化疗+复方M组	46.51±2.33^bc	5.46±0.48^bc	21.36±1.93^bc
化疗+复方H组	39.44±2.27^bcd	3.88±0.20^bcd	17.61±1.58^bcd
F	125.597^＊＊	444.470^＊＊	56.385^＊＊