Study On The Mechanism Of Metabolism Of Triglyceride By SREBP1 And PPARα

Objective:To observe the effect of Qushi Huazhuo Decoction on hyperlipidemia SD rats’blood lipids、liver function and kidney function; To observe the effect of Qushi Huazhuo Decoction on lipid content in the liver; To investigate the possible molecular mechanism of Qushi Huazhuo Decoction on the regulation of triglyceride.Methods:96 healthy male SD rats (190-210g), adaptive feeding for 3 days, randomly selected 18 rats as blank group, for the rest of the hyperlipidemia rats and control group received normal diet and the rest given high fat diet feeding. After 4 weeks of feeding, arrogant in angular vein plexus take blood lipid levels, four rats were sacrificed and take the liver tissue by oil red O staining which was used to observe the lipid content in the liver tissue. After modeling, the rats fed with high fat diet divided into 6 groups:model group, simvastatin group, Gynostemma group, low Qushi Huazhuo Decoction group, middle Qushi Huazhuo Decoction group, high Qushi Huazhuo Decoction group. Continuous intragastric administration for 12 weeks. Every 4 weeks from rat medial venous plexus of blood lipid level detection, body weight was recorded weekly for 1 times. After 12 weeks of treatment in rats. Detection of blood lipids, liver and kidney function. Liver tissues were stained with oil red O staining to observe the morphological changes of the liver tissues. Real time quantitative PCR detection of SREBP1, ACC, PPAR, HSL gene expression.Result:1. Blood lipids: Before treatment, blank group compared with model group, there was a significant difference in serum triglyceride (P<0.05).After 4 weeks of treatment, high fat diet feeding the rats triglyceride levels were compared with the previous rise, blank group and the other groups there were statistically significant differences (P< 0.05); Gynostemma group and the model group, low dose group compared with significant difference (P< 0.05).After 8 weeks of treatment, medium dose group and the model group, the more significant difference, middle dose group rats triglyceride levels decreased significantly (P< 0.05); compared with the blank group and the model group, Gynostemma group, low dose group, a statistically significant difference (P< 0.01), middle dose group, high dose group and blank group no statistical difference (P> 0.05).After 12 weeks of treatment, compared with model group, simvastatin group and gynostemma group were not significant difference (P> 0.05). The other groups had significant difference (P<0.05), which has the strongest effect for middle dose group, followed by high dose group and low dose group. After treatment, there was no significant difference between the low, middle and high dose of traditional Chinese medicine group (P>0.05). There was significant difference between the statin group and the blank group (P<0.05), and there was no significant difference between the other groups (P>0.05). Gynostemma group and blank group and middle dose group had significant difference (P< 0.05), the triglyceride level in middle dose group was significantly lower than the Gynostemma group.2. Liver and kidney function:After 12 weeks, the levels of BUN, ALT, Cr and ASL were detected in the serum of rats. There was no significant difference among all groups(P>0.05).3. Weight:After 12 weeks of treatment, compared with model group, middle dose group and high dose group, the weight is significantly decreased, with a significant difference (middle dose group (P< 0.05). High dose group, P< 0.01, P= 0.008).4.Rat liver tissue SREBP1, ACC, PPAR, HSL gene expression:After 12 weeks of treatment, the objective gene expression in the rat liver tissues were detected and SREBP1. Blank group and model group, atorvastatin group, Gynostemma group have significant difference (P< 0.01). In the low dose group, middle dose group, high dose group and model group decreased compared the, showed statistically significant differences (P < 0.05); the ACC, Gynostemma group and the blank group, middle dose group and high dose group compared with significant difference (P< 0.05), model group and gynostemma group compared with statistical difference, low dose group and model group comparison although downward trend, but no significant difference (P> 0.05).PPAR alpha, the blank group compared with atorvastatin group, Gynostemma group, middle dose group and high dose group, there was significant difference (P<0.05), low dose group, middle dose group and high dose group compared with the model group had a tendency to rise, there are significant differences in high dose group (P<0.05); HSL. Compared with the blank group Gynostemma group, middle dose group and high dose group, there was significant difference (P<0.01), Gynostemma group, atorvastatin group, low dose group, middle dose group and high dose group compared with the model group had a tendency to rise, the Gynostemma group (P<0.05), middle dose group (P<0.01), high dose group (P<0.01) there is a significant difference compared with the model group.5.Oil red O stain:The liver tissue of the blank group was complete, the cells arranged neatly, and the boundary was clear. In the model group, the red dye in the liver tissue was significantly increased, and the morphology and structure of hepatic cells were different. Compared with the model group, simvastatin group and mediun dose group were significantly decreased, and the content of red dye in the low, medium and high dose group was decreased.Conclusion:1. SD rats with high fat diet for 4 weeks can be successfully induced hyperlipidemia model, with significant elevation of serum TG level and pathological changes of liver tissue.2. Huazhuo dampness can effectively regulating TG metabolism in hyperlipidemic rats, and can improve the pathological changes of liver tissue, the effect of middle dose group of the best, and the effect of simvastatin had no significant difference between, and is better than that of Gynostemma Pentaphyllum (Thunb.) control group.3. Qushi Huazhuo decoction can regulating TG metabolism and does not cause liver and kidney function damage. No liver and kidney toxicity.4. Huazhuo dampness may be through inhibition of hyperlipidemia rats SREBP1 expression and a decrease in TG synthesis; and by increasing the expression of PPAR alpha, HSL, the TG increased decomposition, which plays an important role in regulating lipid metabolism and SREBP1, PPAR alpha, HSL may are effective targets of Huazhuo dampness regulation TG metabolism disorders.