The Application Of Deep Low-temperature Optical Imaging In The Research Of Type 2 Diabetes Mice

Observations of organism physiological structure and energy metabolism in various organs and tissues are of great significance in understanding physiological functions,revealing pathogenesis of related disease as well as developing innovative medical approaches and drugs.Through combination of mechanical milling and optical imaging,deep low-temperature micro-optical imaging technology has become a new biology research tool by breaking the limitation of image depth and is therefore able to acquire 3D structural and metabolic information of tissue fixed in vivo under low temperature.In this thesis,physiological structure and energy metabolism change of kidney in the course of type 2 diabetes mellitus was studied using low temperature in vivo fixation and deep lowtemperature micro-optical imaging technology.The thesis selected db/db mice as a model of type 2 diabetes mellitus,explored the changes of renal physiological structure,and the reason for mice kidney structural damage,later found to be hydronephrosis caused by diabetic cystic disease,was revealed.The distribution of hydronephrosis in the kidneys of different diabetic mice were explored,and we found hydronephrosis distribution area in kidney expanded with the increase of age.The phenomenon indicated more intense physiological structural changes along with the course of diabetes mellitus.The thesis then explored energy metabolism changes in physiological-structure-changed mice kidneys by obtaining information on energy metabolism in kidneys from agevaried db/db mice and normal mice.Through comparative data analysis,results were observed.First,energy metabolism activities of normal mice started by decrease followed by stability.Second,energy metabolism activities of the db/db mice showed a tendency to increase after decrease at the beginning.Third,there was difference between energy metabolism of same-aged db/db mice and normal mice.From the results above it can be concluded that energy metabolism in kidney of db/db mice was abnormal in the course diabetes,and oxidative stress occurred in the process.At last,this thesis explored the effects of rhein and betaine on the improvement of energy metabolism and hydronephrosis in db/db mice.It was found that betaine and rhein both have certain positive effect on db/db mice energy metabolism,and the treatment of betaine is more superior.However,both betaine and rhein have no obvious improvement on hydronephrosis.This work also demonstrated that deep low-temperature micro-optical imaging technology is viable in evaluating drug efficacy and is promising in screening drugs for different diseases in the future.This thesis validated the advantages of in vivo low temperature fixation and deep lowtemperature micro-optical imaging technology in obtaining information on biological tissue structure and energy metabolism.Through observing drug efficacy and course change of type 2 diabetes mellitus,it further demonstrated application potential of this new imaging technique in both treatment and prevention of metabolic diseases.