运脾调脂方改善高脂血症大鼠血脂代谢及肝脂肪变性的机制研究

doi:10.11958/20253761

天津医药 ›› 2026, Vol. 54 ›› Issue (6): 585-590.doi: 10.11958/20253761

运脾调脂方改善高脂血症大鼠血脂代谢及肝脂肪变性的机制研究

刘珺¹(), 梁冬丽², 颜琼枝¹^,^△(), 朱逸东¹, 韩天雄¹, 颜乾麟¹

¹ 同济大学附属第十人民医院中医科（邮编200072）
² 上海交通大学转化医学研究院

修回日期:2026-04-09 出版日期:2026-06-15 发布日期:2026-06-15
通讯作者: ^△E-mail：yan_qiongzhi@163.com
作者简介:刘珺（1982），女，副主任医师，主要从事中医心血管疾病及内分泌代谢病方面研究。E-mail：liujune2011@163.com
基金资助:
上海市卫生健康委员会临床研究专项(202340004);转化医学国家重大科技基础设施（上海）开放课题(TMSK-2021-413);第七批全国老中医药专家学术经验继承工作(国中医药人教函〔2022〕76号)

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

LIU Jun¹(), LIANG Dongli², YAN Qiongzhi¹^,^△(), ZHU Yidong¹, HAN Tianxiong¹, YAN Qianlin¹

¹ Department of Traditional Chinese Medicine, the Tenth People's Hospital Affiliated to Tongji University, Shanghai 200072, China
² Translational Medicine Research Institute, Shanghai Jiao Tong University

Revised:2026-04-09 Published:2026-06-15 Online:2026-06-15
Contact: ^△E-mail：yan_qiongzhi@163.com

刘珺, 梁冬丽, 颜琼枝, 朱逸东, 韩天雄, 颜乾麟. 运脾调脂方改善高脂血症大鼠血脂代谢及肝脂肪变性的机制研究[J]. 天津医药, 2026, 54(6): 585-590.

LIU Jun, LIANG Dongli, YAN Qiongzhi, ZHU Yidong, HAN Tianxiong, YAN Qianlin. Study on mechanism of Yunpi Tiaozhi formula in improving lipid metabolism and hepatic steatosis in hyperlipidemic rats[J]. Tianjin Medical Journal, 2026, 54(6): 585-590.

摘要/Abstract

摘要：

目的观察运脾调脂方通过腺苷酸活化蛋白激酶（AMPK）-过氧化物酶体增殖物激活受体（PPAR）α-固醇调节元件结合蛋白（SREBP）轴及相关靶点对高脂血症大鼠血脂水平、肝脏脂质沉积及肝肾功能和血糖（Glu）的影响，评价其有效性及安全性。方法将SPF级SD大鼠60只随机分为空白组，模型组，运脾调脂方低、中、高剂量（0.4、0.8、1.6 g/kg）组及阿托伐他汀组，每组10只。除空白组外，其余组均以高脂饲料联合腹腔注射维生素D3（VitD₃）造模6周，后各组分别给予相应药物灌胃6周。于干预前及末次给药后检测血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、尿素氮（BUN）、血肌酐（Scr）、尿酸（UA）及Glu；对各组进行肝组织病理学观察，并进行非酒精性脂肪性肝病（NAFLD）活动度评分（NAS）；Western blot 检测肝组织脂质代谢关键蛋白。结果治疗前，与空白组比较，模型组及各干预组TC、TG、HDL-C、LDL-C水平均升高（P<0.01）。治疗后，与模型组比较，运脾调脂方各剂量组TC、LDL-C、ALT、Scr、SREBP-1c表达水平均下降，p-AMPK/AMPK及PPARα表达水平均升高（P<0.05），AST、UA和Glu比较差异无统计学意义；高剂量组TG、脂肪变性评分、气球样变评分、小叶炎症评分、NAS总分、BUN下降，阿托伐他汀组Glu水平升高（P<0.05）。各组ALT、BUN、Scr及UA水平均处于正常范围。结论运脾调脂方可通过调控AMPK-PPARα-SREBP轴改善高脂血症大鼠脂质代谢，减轻肝脂肪变性，且对肝肾功能及Glu无不良影响。

关键词: 高脂血症, 脾虚, 血脂异常, 脂肪肝, 运脾调脂方, 痰瘀, AMPK-PPARα-SREBP轴

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

中图分类号:

R589.21

图/表 7

参考文献 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^＊

运脾调脂方改善高脂血症大鼠血脂代谢及肝脂肪变性的机制研究

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

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组别	n	p-AMPK/AMPK	PPARα	SREBP-1c
空白组	9	1.00±0.12	1.00±0.15	1.00±0.14
模型组	9	0.58±0.10^a	0.62±0.11^a	1.68±0.22^a
低剂量组	10	0.72±0.11^b	0.76±0.13^b	1.42±0.20^ab
中剂量组	10	0.85±0.13^b	0.88±0.14^b	1.21±0.18^b
高剂量组	7	0.97±0.15^b	0.95±0.12^b	1.05±0.16^bc
阿托伐他汀组	10	1.02±0.14^b	1.01±0.13^b	0.98±0.15^bc
F		14.632^＊＊	11.284^＊＊	18.907^＊＊

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组别	n		Scr/（μmol/L）				BUN/（mmol/L）
组别	n		治疗前		治疗后		治疗前		治疗后
空白组	9		28.56±4.34		29.00±3.67		6.16±0.68		6.42±1.00
模型组	9		37.67±4.90		55.56±5.73^a		6.87±0.69		7.28±1.22
低剂量组	10		34.40±5.76		33.30±4.71^b		6.34±0.89		6.41±0.93
中剂量组	10		35.90±2.02		33.30±4.47^b		6.25±0.95		6.33±0.95
高剂量组	7		36.57±4.86		32.86±6.04^b		6.21±0.68		5.94±2.00^b
阿托伐他汀组	10		37.70±3.80		57.62±4.30^acde		6.70±0.82		7.11±1.39
F			0.842		6.118^＊＊		1.203		2.457^＊
组别		UA/（μmol/L）				Glu/（mmol/L）
组别		治疗前		治疗后		治疗前		治疗后
空白组		49.37±13.09		81.49±44.02		7.98±1.38		6.13±1.12
模型组		61.26±16.06		81.49±20.82		7.49±1.18		5.36±0.74^a
低剂量组		58.89±13.68		76.73±21.41		7.65±0.81		6.22±1.11
中剂量组		58.29±8.33		63.05±14.87		7.52±1.43		5.97±1.38
高剂量组		65.43±4.76		81.49±19.63		7.99±0.84		6.36±1.31
阿托伐他汀组		63.05±10.11		73.16±19.63		7.34±1.01		6.65±1.35^b
F		1.086		0.731		0.326		3.722^＊＊

组别	n		Scr/（μmol/L）				BUN/（mmol/L）
组别	n		治疗前		治疗后		治疗前		治疗后
空白组	9		28.56±4.34		29.00±3.67		6.16±0.68		6.42±1.00
模型组	9		37.67±4.90		55.56±5.73^a		6.87±0.69		7.28±1.22
低剂量组	10		34.40±5.76		33.30±4.71^b		6.34±0.89		6.41±0.93
中剂量组	10		35.90±2.02		33.30±4.47^b		6.25±0.95		6.33±0.95
高剂量组	7		36.57±4.86		32.86±6.04^b		6.21±0.68		5.94±2.00^b
阿托伐他汀组	10		37.70±3.80		57.62±4.30^acde		6.70±0.82		7.11±1.39
F			0.842		6.118^＊＊		1.203		2.457^＊
组别		UA/（μmol/L）				Glu/（mmol/L）
组别		治疗前		治疗后		治疗前		治疗后
空白组		49.37±13.09		81.49±44.02		7.98±1.38		6.13±1.12
模型组		61.26±16.06		81.49±20.82		7.49±1.18		5.36±0.74^a
低剂量组		58.89±13.68		76.73±21.41		7.65±0.81		6.22±1.11
中剂量组		58.29±8.33		63.05±14.87		7.52±1.43		5.97±1.38
高剂量组		65.43±4.76		81.49±19.63		7.99±0.84		6.36±1.31
阿托伐他汀组		63.05±10.11		73.16±19.63		7.34±1.01		6.65±1.35^b
F		1.086		0.731		0.326		3.722^＊＊