Study on mechanism of Yunpi Tiaozhi formula in improving lipid metabolism and hepatic steatosis in hyperlipidemic rats

doi:10.11958/20253761

Abstract

Abstract:

Objective To investigate the effects of the Yunpitiaozhi formula on the lipid levels, liver lipid deposition, liver and kidney functions and blood glucose (Glu) through the adenylate activated protein kinase (AMPK)?peroxisome proliferator-activated receptor (PPAR) α -sterol regulatory element binding protein (SREBP) axis and related targets in hyperlipidemic rats, and to evaluate its efficacy and safety. Methods Sixty SPF-grade SD rats were randomly divided into the blank group, the model group, the low, medium and high-dose groups of the Yunpitiaozhi formula (0.4, 0.8 and 1.6 g/kg), and the atorvastatin group. Each group consisted of 10 rats. Except for the blank group, all groups were induced with high-fat diet combined with intraperitoneal injection of vitamin D₃ for 6 weeks. Then, each group was given the corresponding drug by gavage for 6 weeks. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA) and Glu were detected before and after the intervention. Liver tissue pathological observation was conducted for each group, and the non-alcoholic fatty liver disease (NAFLD) activity score (NAS) was evaluated. Western blot assay was used to detect key proteins of lipid metabolism in liver tissue. Results Before treatment, compared with the blank group, the TC, TG, HDL-C and LDL-C levels were increased in the model group and all intervention groups (P<0.01). After treatment, compared with the model group, the expression levels of TC, LDL-C, ALT, Scr and SREBP-1c decreased in each dose group of the Yunpitiaozhi formula, and the p-AMPK/AMPK ratio and PPARα expression level increased (P<0.05). There were no statistically significant differences in AST, UA and blood glucose between the groups. In the high-dose group, TG, steatosis score, ballooning score, lobular inflammation score, NAS total score and BUN decreased, and the Glu level increased in the atorvastatin group (P < 0.05). The ALT, BUN, Scr and UA levels were within the normal range in each group. Conclusion Yunpitiaozhi formula can improve lipid metabolism in hyperlipidemic rats by regulating the AMPK-PPARα-SREBP axis, alleviate liver steatosis, and has no adverse effects on liver and kidney functions and blood glucose.

Key words: hyperlipidemias, spleen deficiency, dyslipidemias, fatty liver, Yunpi Tiaozhi formula, phlegm stasis, AMPK-PPARα-SREBP axis

CLC Number:

R589.21

Figures/Tables 7

References 22

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组别	n		TC				TG
组别	n		治疗前		治疗后		治疗前		治疗后
空白组	9		2.99±0.95		3.07±1.04		0.43±0.09		0.39±0.05
模型组	9		12.05±2.77^a		11.47±4.46^a		0.94±0.23^a		0.94±0.17^a
低剂量组	10		12.20±3.35^a		7.62±2.00^ab		0.86±0.31^a		0.78±0.38^a
中剂量组	10		10.59±2.97^a		7.26±1.07^ab		0.91±0.32^a		0.77±0.28^a
高剂量组	7		11.13±4.36^a		7.86±2.78^ab		0.85±0.28^a		0.48±0.18^b
阿托伐他汀组	10		11.36±2.21^a		7.33±1.56^ab		0.71±0.34^a		0.62±0.15^ab
F			13.459^＊＊		11.839^＊＊		4.268^＊＊		5.438^＊＊
组别		HDL-C				LDL-C
组别		治疗前		治疗后		治疗前		治疗后
空白组		1.90±0.66		1.92±0.79		0.20±0.06		0.31±0.10
模型组		3.29±0.86^a		3.51±0.86^a		10.00±2.94^a		8.85±4.97^a
低剂量组		3.51±0.72^a		3.23±0.52^a		7.34±3.40^a		4.88±2.41^ab
中剂量组		2.99±0.47^a		3.26±0.81^a		7.77±3.63^a		4.41±1.21^ab
高剂量组		3.16±0.67^a		3.07±0.75^a		9.12±5.02^a		5.72±2.99^ab
阿托伐他汀组		3.29±0.89^a		2.79±0.92^ab		9.26±4.46^a		5.02±1.23^ab
F		5.762^＊＊		5.062^＊＊		9.186^＊＊		9.758^＊＊

组别	n		TC				TG
组别	n		治疗前		治疗后		治疗前		治疗后
空白组	9		2.99±0.95		3.07±1.04		0.43±0.09		0.39±0.05
模型组	9		12.05±2.77^a		11.47±4.46^a		0.94±0.23^a		0.94±0.17^a
低剂量组	10		12.20±3.35^a		7.62±2.00^ab		0.86±0.31^a		0.78±0.38^a
中剂量组	10		10.59±2.97^a		7.26±1.07^ab		0.91±0.32^a		0.77±0.28^a
高剂量组	7		11.13±4.36^a		7.86±2.78^ab		0.85±0.28^a		0.48±0.18^b
阿托伐他汀组	10		11.36±2.21^a		7.33±1.56^ab		0.71±0.34^a		0.62±0.15^ab
F			13.459^＊＊		11.839^＊＊		4.268^＊＊		5.438^＊＊
组别		HDL-C				LDL-C
组别		治疗前		治疗后		治疗前		治疗后
空白组		1.90±0.66		1.92±0.79		0.20±0.06		0.31±0.10
模型组		3.29±0.86^a		3.51±0.86^a		10.00±2.94^a		8.85±4.97^a
低剂量组		3.51±0.72^a		3.23±0.52^a		7.34±3.40^a		4.88±2.41^ab
中剂量组		2.99±0.47^a		3.26±0.81^a		7.77±3.63^a		4.41±1.21^ab
高剂量组		3.16±0.67^a		3.07±0.75^a		9.12±5.02^a		5.72±2.99^ab
阿托伐他汀组		3.29±0.89^a		2.79±0.92^ab		9.26±4.46^a		5.02±1.23^ab
F		5.762^＊＊		5.062^＊＊		9.186^＊＊		9.758^＊＊

组别	n	脂肪变性评分	气球样变评分	小叶炎症评分	NAS 总分
空白组	9	0.36±0.27	0.05±0.08	0.38±0.36	0.77±0.37
模型组	9	2.46±0.47^a	1.65±0.38^a	1.77±0.60^a	5.88±0.60^a
低剂量组	10	2.10±0.40^a	1.14±0.41^a	1.31±0.39^a	4.54±0.71^a
中剂量组	10	2.23±0.43^a	1.15±0.37^a	1.25±0.15^a	4.64±0.64^a
高剂量组	7	1.49±0.26^abcd	0.73±0.17^ab	1.05±0.37^ab	3.28±0.49^abcd
阿托伐他汀组	10	1.05±0.60^abcd	0.49±0.32^abcd	0.65±0.43^abcd	2.18±0.86^abcd
F		35.431^＊＊	37.480^＊＊	12.125^＊＊	70.600^＊＊

组别	n	脂肪变性评分	气球样变评分	小叶炎症评分	NAS 总分
空白组	9	0.36±0.27	0.05±0.08	0.38±0.36	0.77±0.37
模型组	9	2.46±0.47^a	1.65±0.38^a	1.77±0.60^a	5.88±0.60^a
低剂量组	10	2.10±0.40^a	1.14±0.41^a	1.31±0.39^a	4.54±0.71^a
中剂量组	10	2.23±0.43^a	1.15±0.37^a	1.25±0.15^a	4.64±0.64^a
高剂量组	7	1.49±0.26^abcd	0.73±0.17^ab	1.05±0.37^ab	3.28±0.49^abcd
阿托伐他汀组	10	1.05±0.60^abcd	0.49±0.32^abcd	0.65±0.43^abcd	2.18±0.86^abcd
F		35.431^＊＊	37.480^＊＊	12.125^＊＊	70.600^＊＊

组别	n		ALT
组别	n		治疗前		治疗后
空白组	9		48.27±11.12		60.41±26.94
模型组	9		127.82±44.05^a		121.17±56.78^a
低剂量组	10		94.98±36.08^a		73.12±31.50^b
中剂量组	10		96.74±32.39^a		72.08±30.57^b
高剂量组	7		97.70±25.58^a		75.83±27.96^b
阿托伐他汀组	10		92.22±45.67^ab		110.43±42.87^a
F			3.479^＊＊		2.436^＊
组别		AST
组别		治疗前		治疗后
空白组		85.61±31.67		91.24±30.48
模型组		134.18±34.34^a		168.41±49.88^a
低剂量组		116.91±28.95^a		130.55±31.97^a
中剂量组		113.24±21.17^a		133.92±32.16^a
高剂量组		110.17±22.73^a		137.21±45.92^a
阿托伐他汀组		114.14±42.18^a		148.88±56.60^a
F		2.644^＊		3.305^＊