The Study Of Mechanisms Of Xiao-Yao-San Influencing IR In T2DM Mouse By Chronic-Psycho Logical-Stress

ObjectiveDiabetes is the third important mental and physical disease preceded only by thd heart-brain artery and cancer. It’s incidence surpass9.7%. T he disease number of people reach about100million. Now China is the max country of diabetes people in the world. Among exceeding90%is Type2diabetes. T2DM and it’s complications have becomed the serious psychologi cal-physical problem to threaten the humanity. The new medicical mode of organism-psychology-society consider that the diabetes is a kind of the p sychological and physical disease. Psychological sensitive is the importa nt inducing factor. And the social and psychological factors have given t o value by the people, which is indentical with "feeling disese" of the theory of the traditional Chinese medicine.The occurrence of insulin resistance is surpass80%in T2DM. IR is o ne kind of the primary disease mechanism. It appears the whole process of the happening and development in the T2DM, At the same time, it is also the important pathological foundation of many metabolic diseases such as obesity, hypertension and hyperlipdimia and so on. But now, IR’s patholog ical mechanism is very complex and vague. So reseaching IR, especially st udying it’s occurrence mechanism from the direction of combining traditio nal Chinese and Western medicine, which it is not only enrich the theory of traditional Chinese and Western medicine, but also can prevent and cur e many metabolic diseases.The study put forward to a important hypothesis, that the diabetes’s basic phthogenesis is the spleen can not generate the essence, according t o the diabetes clinical characteristic and feeling disease theory. The st udy object is spontaneous diabetes mouse, method is pathology, molecular biology, and from the sugar-substitution and gene to probe the the mechan ism of the mental sensitive influence IR and the effect mechanism of the compound prescription of Xiao-yao power medicine.MethodsThe study uses male KK mouses, feeding the fodder of hyperglycemia-hy perlipidemia for8weeks to build the model of T2DM. Using electric-shock, clamping the tail,not eating, not water and so on, to build the model of ch ronic-psychological-stress. The purposes to observe the Xiao-Yao-San’s eff ect to biochemistry index of chronic—mental-irritable T2DM mouses, the e ffect to gene express of chronic-psychological-stress T2DM mouses, the ef feet to glucocorticosteroid receptor(GR) express and IRS-1express of chr onic-psychological-stress T2DM mouses.Results1The Xiao-Yao-San’s effect to biochemistry index of chronic--psychol ogical-stress T2DM mousesCompare to WC-group, SC-group mouses’FBG raise, HbAlc ascend and ISI descend clearly. Their’s body weight reduce, TG、CHO ascend and HDL-C desc end. But the XYS-group are opposited. To compare SC-group, the groups’of S+LXYS and S+HXYS FBG and HbAlc descend, the body weight ascend, TG,CHO,L DL-C descend and HDL-C ascend clearly.2The Xiao-Yao-San’s effect to gene express of chronic--psychological-stress T2DM mousesAmong89related genes, comparing to WC-group, there7genes ascend, FO XC2、Ifng、IL-10、Sell、Slc2a4、Tnf and Ucp2and6genes descend, Aqp2, Cc r2、FOXg1、F0XP3、Pfkfb3、Tnfrsflb in SC-group. There are8genes ascend, A dral-α、FOXC2、Ifng、Neurodl、Nsf、Pparg、Slc2a4、Gusb and3genes descen d, Aqp2、Pfkfb3、Tnfrsf1in XYS-group. Comparing to SC-group,there are2g enes ascend, FOX P3、Ppargcla,4genes descend, Ace、IL-10、Slc2a4, Aktb in S+LXYS-group. There are37genes ascend, Ac1y、Adral-α、Aqp2、DPP4、Fbp1、 G6PC、Gpd1、Icaml、Igfbp5、IL-4ra、Insl、Mapkl4、Nfkb1、Nos3、Nrf1、Nsf、P arpl、Pik3cd、Ppara、Pparg、Ptpn1、Pyg1、Rab4a、Slcl4a2、Snap23、Sod2、Sre bf1、Stxbp1、Tnfrsfla、Trib3、Ucp2、Vamp3、Yapa、Hprt、Hsp90abl,6descend genes, Adra3-β、GlPlr、Vegfa、Actb、Snap25、Pax4.3The Xiao-Yao-san’s effect to GR express of chronic-psychological-s tress T2DM mouses 3.1the GR express difference in insulin cells of all groupsAnalysis from morphology, SC-group’s fluorescence strength is the bes t intheinsulin, and the better is WC-group, and in order is S+LXYS and S+HXYS groups, the weakest is XYS-group. Analysis from statistical data, th e results are the same, that is comparing WC-group, SC-group’s GR express in insulin cells ascend clearly, and XYS-group is opposite results. Comp are SC-group, GR express in insulin of S+LXYS and S+HXYS groups are desce nd.3.2the GR express difference in liver cells of all groupsAnalysis from morphology,the fluorescence strength is followed from s trong to weak, WC-group, S+HXYS group,XYS-group, S+LXYS-group and SC-group. The micro-structures are different. The liver-cell structures are intact of WC-group, but the array are not rule and the radioactive liver-rope st ructure are fuzzy. The liver-cell array are rule and radioactive liver-ro pe structure are clear of XYS-group. But the liver-cell array are disorde r and infrequent and have many bubbles. The liver cell array and numbers are better than SC-group. Analysis from statistical data, comparing WC-gr oup, GR express in liver cells ascend clearly of SC and XYS group. Compar ing SC-group, GR express in liver cells of S+LXYS and S+HXYS groups are a scend clearly. But the two groups are lower than WC-group.4The Xiao-Yao-San’s effect to IRS-1express of chronic-psychologica1-stress T2DM mouses4.1the IRS-1express difference in insulin cells of all groupsAnalysis from morphology, the green fluorescence strength of XYS, S+LX YS and groups are clearer than WC and SC groups. Analysis from statistica1data, comparing WC-group, IRS-1express in insulin cells descend and as cend of SC group. Comparing SC-group, IRS-1express in insulin cells of a re ascend of S+LXYS and S+HXYS groups.4.2the IRS-1express difference in liver cells of all groupsAnalysis from morphology, the green fluorescence strength of S+HXYS,X YS, and S+LXYS groups are clear and the liver array are rule and liver ro pe clear,but the green fluorescence strength of WC and SC groups are weak and the liver cells array disorder and liver rope structures fuzzy. Anal ’sis from statistical data, comparing WC-group, IRS-1express in liver ce lls descend of SC-group and ascend of XYS-group. Comparing SC-group, IRS- 1express in liver cells are ascend of S+LXYS and S+HXYS groups, between the S+HXYS group is clearer.conelusions1Chronic-psychological-stress can make more serious hyperglycemia f or T2DM, reduce insuline sensitivity, raise TG、CHO,reduce the body weight. XYS-power’effect lies in the following:one aspect can descend the gluco se,the second can resist the hyperglycemia resulted from Chronic-psycholo gical-stress, ascend insuline sensitivity, reduce TG、CHO、LDL-C, ascend HDL-C, and reduce hyperlipidemia and body weight becaused of Chronic-psychol ogical-stress. It’s effect mechanism might have increased insuline sensit ivity to correct the sugar-fat disorder.2Because of the variegation and heterogeneity of T2DM heredity, the re is not proper, comprehensive, suitable technology and heredity analysis methods for gene-heredity diseases. The study selects89related gene of T2DM, uses PCR microchip technology to probe the influence of Chronic-psyc hological-stress to IR of T2DM and Xiao-Yao-San effect machnism. Result:c omparing to WC-group,there is7genes ascending,6genes descending of SC-group; there is8genes ascending,3genes descending of XYS-group; among FOXC2、Ifng、Slc2a4are their common ascending genes. Aqp2、Pfkfb3. Tnfrsf1b are their common descending genes.So, Chronic-psychological-stress can adjust related genes express and make more serious IR of T2DM. Xiao-Yao-San can prevent and cure diabetes and improve IR, Which it is might relate d to genes express.3Chronic-psychological-stress can increase GR express in insulin ce11of T2DM mouses.But Xiao-Yao-San can reduce GR express in the insulin c ell of T2DM. S+LXYS and S+HXYS groups all can reduce GR express in insulin cell of Chronic-psychological-stress T2DM, and S+HDL-C group’s effect is better than S+LXYS group. But GR express in liver cell of SC-group is desc end, that can relate to liver cell death resulted from long-time Chronic-p sychological-stress.GR express in liver cell of S+LXYS and S+HXYS groups are ascend, and S+HXYS group’s effect is better than S+LXYS group, which it might be Xiao-Yao-San make better liver cell damage becaused of Chronic-psychol ogical-stress.4Chronic-psychological-stress can decrease IRS-1express in insulin cell of T2DM mouses.But Xiao-Yao-San ascend IRS-1express in insulin cel l and liver cell of T2DM mouses, that the result is the same to the gene e xpress. The result is to show that inhibiting IRS-1express in insulin ce ll,reducing insulin secretion, and inhibiting IRS-1express in liver cell, reducing liver glycogen’s compound might be important effect mechanism of IR of T2DM mouses resulted from Chronic-psychological-stress. Xiao-Yao-S an can ascend IRS-1express in insulin and liver cells, increase insulin s ectetion, increase liver glycogen’s compound to reduce glucose and relieve insulin resistant.