Experimental Study On The Lipid-lowering Effect Of Gualou Xiebai Banxia Decoction In Hyperlipidemia-like Rats Induced By Poloxamer 407

Objectives:In the study,poloxamer 407 were used to induced the model of hyperlipidemia in rats,and the effects of Gualou Xiebai Banxia Decoction on abnormal blood lipid metabolism,liver steatosis,and glucose tolerance and the m RNA expression of MTTP,FAS,ACC and SCD1 in liver tissues,explore the effect and mechanism of Gualou Xiebai Banxia Decoction in regulating hyperlipidemia,so as to provide a scientific basis and dates for the clinical application of Gualou Xiebai Banxia Decoction and the development of in-hospital preparations.Methods:The 5-to 6-week-old Wistar male rats were selected to prepare hyperlipidemia model and randomly divided into two drinking groups: one group was gavaged dosed orally with Gualou Xiebai Banxie Decoction,and the other group was gavaged equal volume of pure water,respectively.The hyperlipidemia model was prepared by intraperitioneal injection of Poloxamer 407,and according to their plasma lipid levels and body weight changes,rats with successful modeling were screened and divided into Control group,P407 group and GLXBBX group.Twenty-eight days after intraperitoneal injection Poloxamer 407 and intervention with Gualou Xiebai Banxia Decoction,the changes of oral glucose tolerance(OGTT),plasma lipid levels of triglycerides,total cholesterol,low density lipoprotein and high density lipoprotein were detected by automatic biochemical analyzer,the liver histopathological changes were observed by using H&E staining and the liver lipid accumulation by using oil red staining,plasma lipoprotein lipase activity were tested by using Elisa assay,and the m RNA expressions of MTTP,FAS,ACC and SCD1 in liver tissue were measured by q RT-PCR.Results:(1)Compared with the Control group,the level of plasma triglycerides and total cholesterol in the P407 group increased 133 % and 26.9 %(P<0.05),respectively,,the brown fat to body weight ratio in P407 group increased 26.9 %(P<0.05),the plasma lipoprotein lipase activity in the P407 group decreased 30 %(P<0.01);compared with the P407 group,the plasma triglyceride level of the GLXBBX group decreased 40.8 %(P<0.05),and the plasma high-density lipoprotein level increased47.8 %(P<0.05),the brown adipose tissue to body weight ratio in GLXBBX group decreased 21.2 %(P<0.05),the plasma lipoprotein lipase activity increased 35.7 %(P<0.05);(2)Compared with the Control group,the liver weight/body weight ratio in the P407 group increased 10.4 %(P<0.05),the hepatic triglyceride level of the P407 group increased 162.5 %(P<0.05),the alanine aminotransferase and aspartate aminotransferase to alanine aminotransferase ratio in the P407 group increased53.1 % and 25.3 %(P<0.05),respectively,the m RNA expression of FAS and SCD1 in the liver tissue of the P407 group raised 222 % and 116%(P<0.05),respectively;compared with the P407 group,the liver weight/body weight ratio in the GLXBBX group decreased 23.9 %(P<0.001),there was a decreasing trend in the hepatic triglyceride and total cholesterol levels of GLXBBX group,but the difference was not statistically significant(P>0.05),both the alanine aminotransferase and aspartate aminotransferase to alanine aminotransferase ratio in the P407 group decreased 33%(P<0.05),the m RNA expression of SCD1 in the liver tissue of the GLXBBX group decreased 89.3 %(P<0.05),the m RNA expression of MTTP in the liver tissue of the GLXBBX group increased(P<0.01);the H&E staining showed that the normal hepatocytes were almost invisible in the liver tissue of the P407 rats,enlarged hepatocytes,disordered hepatic cord,and numerous fat vacuoles and lightly stained in the cytoplasm of the GLXBBX group were observed;compared with the P407 group,the hepatic lipid accumulation of the GLXBBX group was significantly reduced;(3)Compared with the Control group,the random blood glucose of the P407 group increased 18.1 %,and the glucose tolerance was impaired(P<0.05).Conclusions:(1)Gualou Xiebai Banxia Decoction could decrease the elevated Plasma triglyceride of hyperlipidemia induced by Poloxamer 407.Gualou Xiebai Banxie Decoction could improve the huperlipidemia induced by Poloxamer 407 through increasing the reduced content of brown fat induced by Poloxamer 407,promoting the secretion of lipoprotein lipase and activate it,and accelerating the plasma triglyceride metabolism.(2)Gualou Xiebai Banxia Decoction could rectify the hepatic lipid accumulation and regulate hepatic steaosis by improving hepatic disfunction induced by Polocamer 407,decreasing the levels of Plasma alanine aminotransferase and asparate aminotransferase.Gualou Xiebai Banxia Decoction could inhibit the Ch REBP signal transduction in the liver tissue,thereby inhibiting the m RNA expression level of SCD1 induced by Poloxamer 407 and suppressing the synthesis of triglyceride metabolism;Gualou Xiebai Banxia Decoction could promote the m RNA expression levels of MTTP and the tranfer triglyceride and phospholipid cholesterol ester to newborn apoprotein B(apo B),and mediate the assembly of very low density lipoprotein(VLDL)and chylomicrons in liver and intestine.(3)Poloxamer 407 could increase random blood glucose and induce impaired glucose tolerance.