| Metabolic syndrome (MS), as a group of symptoms associated with the metabolism has recently become a mutual hot topic in medical multidiscipline research and is generally considered to have insulin resistance as the pathological core area, obesity an important inducing factors, and inflammation an important pathological feature. The pathogenesis of MS is usually manifested by abnormal aerification, qi activity disorder, body fluid distribution, as well as dampness and phlegm stagnation, which is closely related to the physical functions of triple-jiao. In line with the determination of etiologic factors based on differentiation and treatment based on etiology, and according to the pathogenesis features of MS, one should therefore treat MS from the aspect of triple-jiao. Chaihu Modified Longgu Muli Decoction is a classic formula for discharging triple-jiao and the modern pharmacological studies have also indicated that the main ingredients within show good effects in anti-inflammation, decreasing blood lipid and sugar. Hence, the effects of Chaihu Modified Longgu Muli Decoction in the management of MS is worth being further studied and analyzed.ObjectivesTo observe the protective effects of Chaihu Modified Longgu Muli Decoction on MS model rats and to probe into its mechanism with molecular biology methods and to provide theories and experimental foundations for the prevention of MS with Chaihu Modified Longgu Muli Decoction, so as to further explore ways and methods to prevent and manage MS.MethodsAfter MS rats modeling, Chaihu Modified Longgu Muli Decoction was used as an intervention. Five steps as follows were included in the experiment:1.The MS rat models were established after administration of high sugar, lipid and salt diets for16wks. The levels of fasting blood glucose, lipid, serum insulin and HOMA-IR, as well as Lee’s index were determined to evaluate rats modeling successful or not.2.The effects of Chaihu Modified Longgu Muli Decoction on MS model rats glucose and lipid metabolism were observed thorough differences indicated in levels of fasting blood glucose, TG, TC, HDL-C ad HOMA-IR of rats from varied groups, so as to explore its prevention and management of MS and the relevant mechanism.3.The effects of Chaihu Modified Longgu Muli Decoction on model rats inflammatory factors were observed by differences between TNF-a and IL-6in each group in order to figure out its anti-inflammatory mechanism and to analyze the interventions. 4.The effects of Chaihu Modified Longgu Muli Decoction on model rats PI3K pathway were evaluated thorough observing differences in model rats diaphragm IRS-1protein and GLUT4protein expression from each group with Western blot so to explore Chaihu Modified Longgu Muli Decoction’s intervention on MS.5.The toxicity of Chaihu Modified Longgu Muli Decoction was determined with model rats blood lead levels, hepatorenal functions and biopsy HE staining.Results1.The MS model rats were established successfully. The model rats showed significant increase in body weight(P<0.01), length(P<0.01), FBG(P<0.01), diastolic pressure(P<0.05), serum insulin(P<0.01), TC(P<0.01), TG(P<0.05), HDL-C(P<0.05), Lee’s index(P<0.01), and HOMA-IR values(P<0.01),which met the MS characteristics and was in line with modelling requirement.2.The FBGs in model rats from high dose, middle dose and positive drug groups decreased obviously, with significant difference with model group (P<0.01). The levels of serum insulin and HOMA-IR in positive drug, high does and middle dose groups showed significant difference with model group (P<0.01); serum insulin of the low dose group decreased significantly with comparison to model group (P<0.05). TG index of high dose group increased significantly with comparison to model group (P<0.01); TG index of the middle dose group showed statistic difference with model group (P<0.05). TC index in positive drug, high dose, middle dose and low dose groups decreased with significant differences between the high, middle doses groups and model groups (P<0.01), positive drug, low dose and model groups showing statistic difference (P<0.05). LDL-C and HDL-C levels of high groups decreased significantly with comparison to the model group(P<0.05).3.TNF-a and IL-6levels in high and middle dose groups showed significant differences with comparison to model group (P<0.01), low dose group showing statistic difference with model group (P<0.05). IL-6in low dose group decreased significantly with comparison to model group(P<0.01), diet group showing statistic difference with model group (P<0.05).4.Western blot (WB) demonstrated that:rats IRS1expression in positive, high dose groups was increased, with significant difference with model group (P<0.01); rats IRS1expression in middle dose group was also improved with statistic difference to model group (P<0.05). GLUT4expression in positive, high dose and middle dose groups was increased with significant difference to model group (P<0.01). Immunohistochemical staining demonstrated that active IRS1and GLUT4expression in positive, high dose, middle dose and low dose groups, with statistic differences to model group (P<0.01); diet group also showed statistic difference in IRS1integrated optical density with comparison to model group (P<0.05).5.It was also demonstrated that lead content varied respectively in each group with Chaihu Modified Longgu Muli Decoction intervention but within the normal range; renal function and HE staining were normal; liver function and HE staining showed differences with no significant difference in control group.Conclusion1. A high lipid, sugar and salt diet intervention on SD rats can contribute to the MS model rats.2. Chaihu Modified Longgu Muli Decoction can regulate indicators of fasting blood glucose and lipids of MS model rats, suggesting a good intervention effects on sugar and lipid metabolism of MS model rats.3. Chaihu Modified Longgu Muli Decoction can decrease TNF-a and IL-6levels and effectively inhibit the release of inflammatory factors, indicating its good intervention functions on the inflammatory state of MS model rats4. Chaihu Modified Longgu Muli Decoction can improve IRS-1and GLUT4protein expression, showing its PI3K signal pathway intervention at protein level so as to prevent and manage MS.5. Chaihu Modified Longgu Muli Decoction is safe and the pathological changes in liver is considered resulted from MS.6. The management of MS with Chaihu Modified Longgu Muli Decoction is practical in theory and has been supported by experiments. |
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