Liuwei Dihuang Formula Alleviates Abnormal Lipid Metabolism by Up-Regulating Intestinal Estrogen Receptors in Postmenopausal ApoE^-/- Mice

OBJECTIVE Establish a model of postmenopausal abnormal lipid metabolism in ApoE^-/- mice by bilateral ovariectomy， and to explore whether Liuwei Dihuang formula (LW) can alleviate postmenopausal abnormal lipid metabolism by regulating intestinal estrogen receptors. METHODS C57/B6 mice with a normal diet were used as the control group (n=6)， ApoE^-/- mice with a high-fat diet and receiving sham operations were used as the sham-operated control group (n=6)， ApoE^-/- mice with a high-fat diet and receiving bilateral ovariectomy were used as the model group (n=6)， and the model mice received 4.5 g/kg (n=6) or 9.0 g/kg (n=6) LW for 90 days. Biochemical method was used to detect the levels of TC， TG， LDL-C and HDL-C in the serum of mice， HE staining was used to detect liver lipid damage in mice， oil red O staining was used to detect liver lipid accumulation in mice， immunofluorescence staining was used to detect mouse the expression levels of ERα， ERβ， ABCG5， ABCG8， PI3K p110β and p-AKT in the jejunum of mice， immunochemical staining was used to detect the expression level of NPC1L1 in the jejunum of mice. Western blot was used to detect the expression levels of NPC1L1， ABCG5 and ABCG8 in the jejunum of mice. RESULTS LW could reduce serum TC， TG and LDL-C levels， and increase HDL-C level in model mice（P<0.05， P<0.01）， moreover， LW could significantly reduce liver lipid damage and fat accumulation in model mice（P<0.05， P<0.01）. LW could increase the expression levels of ERα and ERβ in the jejunum of model mice（P<0.05， P<0.01）. LW significantly reduced the expression level of NPC1L1 in the jejunum of model mice（P<0.05）， and increased the expression levels of ABCG5 and ABCG8（P<0.01）. LW significantly increased the expression levels of PI3K p110β and p-AKT in the jejunum of model mice（P<0.05， P<0.01）. CONCLUSION LW can significantly improve the symptoms of abnormal lipid metabolism in postmenopausal ApoE^-/- mice， and its mechanism may be related to the regulation of the intestinal cholesterol efflux and absorption. The up-regulated expression of intestinal estrogen receptor and PI3K/AKT signal in intestine may be the mechanism that how LW regulates intestinal cholesterol efflux and absorption.