| Diabetes is an endocrine disturbance threating to human's health, always follows to the periphery tissues' depression of insulin and indiscriminate regulation of insulin's signal's pathway. A very important mechanism of regulation is reversible tyrosine phosphorylation to the insulin receptor, insulin receptor's substrate and their downstream molecule's protein. These years' studies show that protein tyrosine phosphatase 1B (PTP1B) is an important negative accommodation to the insulin receptor and the receptor's substrate. Inhibiting the activity of PTP1B will help to elevate the periphery tissues' sensitivity to the insulin, so PTP1Bi has a good prospect in diabetes' treatment.For having very important regulation effect in sorts of cells' signal's pathway, PTP already has the qualification to be the target of pharmaproject. The PTP1B inhibition's pathway is a sophisticated process, which mainly consist of: straight inhibition of the activity point; inhibition of oxidation;the regulation of the protein's expression in gene-level. Some compositions of extractive from traditional Chinese drugs also have PTP1B inhibiting activity .Flavonoids,triterpenoid and multi-pipe alga are the present domestic warm spots in PTP1B inhibition's study. After the former extraorgan screening we found that CMOE has PTP1B inhibiting effect, the inhibition ratio was 86%, so we established T2DM to approach it's effect.The methods in my study: giving high fat diet for 28 days, then injecting small dose STZ in sublingual vein to establish type 2 diabetes models in rats, intragastricing cortex magnoliae officinalis' extract(CMOE) for another 28 days, gathering blood from vena caudalis every week to detect FBG. After 4 weeks' administration, gathering blood from abdominal aorta and abstracting blood serum for the detection of C-peptide,TC,TG,HDL-c,LDL-c,Insulin,C-peptide,IL-6,TNF-α,MDA and the activity of SOD;gathering liver from the same part of all the rats to detect the contents of hepatic glycogen; gathering all rats' pancreas with formalin fixation for immuno-histo-chemical analysis and islet cells' morph observation. As the results showed below: 1, In the model of hyperglycemia rats induced by high fat diet with low-dose STZ, CMOE 75 mg/kg, 150mg/kg, 300mg/kg have decreased FBG significantly at the 4th week compared with the control set ( P <0.01 or P <0.05), the liver glycogen content has the declined tendency, The results have suggested that CMOE could reduce the blood glucose levels significantly, improve the disorders of glucose metabolism in T2DM rats.2, Compared with the model set, the serum TC levels of CMOE 75 mg/kg, 150mg/kg, 300mg/kg sets were decreased significantly (P<0.05 or P<0.01), TG, LDL-c levels of 150mg/kg, 300mg/kg sets decreased significantly (P<0.05), the results have indicated that CMOE could improve the disorders of blood lipid metabolism in T2DM rats.3, The activity of SOD in the model set degraded and the content of MDA increased significantly(P<0.05), the results showed that there is free radical disturbance in type 2 diabetes models. Compared with the model set, after 4 weeks of CMOE, 300 mg / kg has increased the activity of SOD and 150 mg/kg,300 mg / kg decreased the content of MDA significantly in serum (P <0.05), From the result we can conclude that CMOE can increase the activity of SOD in T2DM rats, elevate the models' ability of eliminating free radical, lesson the injure of the body.4, Compared with the normal set, the content of IL-6 and TNF-αin T2DM rats has increased significantly (P <0.05 or P <0.01). Compared with the model set IL-6 of 300 mg/kg has the declined tendency, but not significant. The results suggested that CMOE could somehow ease the inflammatory response in the body.5, Compared with the normal set, the C-peptide levels of T2DM rats were significantly lower, and islet cells were dispersed. The distribution of isletβcells was uneven, and the number of islet cells were decreased significantly, C-peptide levels were significantly increased after administered CMOE, and insulin secretion index (IS) was increased significantly, the damage of islet have better improved.This study has showed that: CMOE could decrease high blood sugar, and therapy type 2 diabetes, it could increase glycogen synthesis, regulate the disorders of glucose and lipid metabolism, reduce the inflammatory response, improve the ability of eliminating free radical , improve isletβ-cell function and enhance the sensibility of insulin, against IR. This research can make a theoretical and experimental basis on the study of CMOE in the further development and application.
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