Research On Regulation Effect Of Shibuwei Heziliniao Pills On The Glycolipid Metabolism Dysfunction In Mice

Glycolipid Metabolism Dysfunction(GMD)diseases such as obesity and hyperinsulinemia can affect the quality and reproductive performance of livestock and poultry.Long-term abnormal glucose and lipid metabolism can cause many complications,damage part of the animal’s organs and lead to the gradual decline of their functions,even cause disability and death.The prescription of Shibawei Heziliniao Pills is derived from "Tibetan Medicine Jue Supplement",which is clinically applied to disorders of glucose and lipid metabolism,kidney disease and other diseases.The preliminary research of our laboratory found that Shibawei Heziliniao Pills could improve glucose and lipid metabolism disorders and brain damage by regulating blood lipids and blood glucose levels and antioxidant efficacy in GMD mice.However,the specific mechanism of Shibawei Heziliniao Pills regulating glucose and lipid metabolism in GMD mice is still unclear.This study uses high-fat and high-sucrose(HFSD)combined with streptozotocin(STZ)to establish a GMD mice model,and explores the eight flavors through Morris water maze,transcriptome sequencing,proteome sequencing,q PCR,WB,HE staining and other methods.The molecular mechanism of Myrobalan Diuretic Pills regulating glucose and lipid metabolism in GMD mice,the screening of target molecules and signal pathways,and the discovery of the mechanism by which Shibawei Heziliniao Pills regulate cognitive impairment caused by GMD mice.This experiment provides a scientific basis for the mechanism of drug regulation of animal glucose and lipid metabolism disorders.The results of this study are as follows:1.Shibawei Heziliniao Pills relieve abnormal glucose and lipid metabolism in GMD mice.The GMD mouse model is constructed by using a high-fat and high-sucrose diet(HFSD)combined with streptozotocin(STZ),after the model is stable,continue to gavage150mg/kg Shibawei Heziliniao Pills for 4 weeks.The results showed that Shibawei Heziliniao Pills could significantly reduce the blood glucose and blood total triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)content in GMD mice(p<0.01);q PCR and WB results showed that Shibawei Heziliniao Pills increased the expression of key enzymes GLUT1,GLUT3,HK1,and α-KGDH in hippocampus of GMD mice(p<0.05)and reduced the expression of anaerobic metabolism key enzymes LDHA and LDHB(p<0.01),increase the expression of lipid synthesis genes FAS,ACC,PPARγ,SREBP1 C in hippocampus,subcutaneous white fat,and palm fat(p<0.01);promote thermogenesis genes UCP1,UCP4,and UCP4 in subcutaneous white fat The expression of PGClα and PRDM16(p<0.01),and the expression of HSL,ATGL and CPT1α(p<0.01)of the lipolytic genes HSL,ATGL and CPT1α in hippocampus,subcutaneous white fat and palm fat were reduced.2.Shibawei Heziliniao Pills can improve glucose and lipid metabolism in GMD mice by inhibiting LRG1 protein in the AGE-RAGE signaling pathway.Through GMD mouse hippocampal transcriptome and proteome sequencing,two omics NC group and DC group,DC group and DCS group,NC group and DCS group differentially expressed genes,proteins and signal pathways were obtained(p<0.01),further screened out the target molecule LRG1,AGE/RAGE signaling pathways,which regulated the glucose and lipid metabolism of hippocampus in GMD mice.3.Shibawei Heziliniao Pills can mitigate cognitive impairment in GMD mice.The water maze experiment,Nissl staining,q PCR and WB experiments were used to explore the regulating effect of Shibawei Heziliniao on the nervous system function of GMD mice.The water maze experiment showed that Shibawei Heziliniao Pills can improve the learning and memory of GMD mice by reducing the escape time and increasing the swimming speed and total distance of model mice(p<0.05);enhance hippocampal synaptic function by increasing the expression of neurotrophic factors BDNF,NGF,NT3 and NT4 and synaptic proteins SNSP-25 and PSD-95(p<0.01);down-regulate the expression of neuroinflammatory factors INOS,COX-2,TNF-α,IL-6(p<0.01)and inhibit neuroinflammation(p<0.01).This research reveals that Shibawei Heziliniao Pills can reduce blood glucose and blood lipids in mice with glucose and lipid metabolism disorders;it proves that Shibawei Heziliniao Pills can alleviate the metabolic disorders caused by high-fat and high-glucose rdiet;clarify Shibawei Heziliniao Pills regulates glucose and lipid metabolism disorders by targeting LRG1 and AGE-RAGE pathways,and improves the cognitive impairment of GMD mice by enhancing learning and memory in GMD mice,inhibiting neuroinflammation;the result of the study is that Shibawei Heziliniao Pills are used The prevention and treatment of glucose and lipid metabolism disorders in livestock and poultry production provides experimental evidence,and provide a theoretical basis for in-depth study of the plasticity regulation of animal glucose and lipid metabolism and the improvement of livestock and poultry reproductive performance.