| Temporomandibular joint disorder is a common disease involving a variety ofpathological changes, including the masticatory muscles and temporomandibular joint. Itcan be caused by many factors, and the etiology can be divided into physiological andpsychological aspects. Physiological factors include occlusal disorders, trauma,autoimmune diseases and etc., while psychological factors are mainly caused by stress. InSpeculand’s opinion, the psychological stresse is an important etiology fortemporomandibular joint dysfunction. Generally speaking, the psychological stress usuallyleads to two psychological changes, anxiety and depression. Depression is a worldwidedisease which has a serious impact on human physical and mental health. With thecontinuous extension of human life, the incidence of depression is continuously increasedin recent years, which is estimated to reach15-20%. Presumably, nearly340millionpeople are suffering from major depression in the world. A large number ofepidemiological investigation about the relationship between depression andtemporomandibular joint disorders have been done in the past decades, and the surveyevidence suggested that there were indeed a correlation between depression and theoccurrence of temporomandibular joint dysfunction. Studies have shown that not only theextent of depression in patients with temporomandibular joint disorder is significantlyhigher than the normal subjects, but also positively correlated with the severity of symptoms. In addition, the muscle dysfunction is more relevant with psychological factorsthan temporomandibular joint or articular disc.The abnormal emotions of temporomandibular joint disorder patients, such as anxiety,depression, can provide bio-psycho-sociological information for clinicians. In order toenhance the effect of treatment and reduce the recurrence, the clinicians should eliminatethe patient’s psychosocial stimulation and give them psychological therapy necessarily.And a large number of studies have found that assisted psychological intervention caneffectively improve the therapeutic effect and reduce disease recurrence.Although there are a lot of documentary evidence supporting the correlation betweendepression and temporomandibular joint disorders, all the studies are basically belong toepidemiological investigation, and mostly are cross-sectional studies. So far, it still lacksof evidence to clarify the mechanisms of temporomandibular joint disorders led bydepression. For the above reasons, the thesis focuses on the masseter muscle changes indepression-like behavior rat caused by stress and the effect of curcumin on it.This topic is divided into four parts as listed below:1、To establish and evaluate the chronic unpredictable mild stress (CUMS) model inrats.We chose7mild stressors to establish a chronic unpredictable stress rat model. The7stressors were randomly applied daily to rats. Mild stress factor can avoid stimulation torats’ body, and a randomized manner is to avoid adaptability of the rats which leads to thereduction of validity of the CUMS model in the long-term process. At end of the process,the rats showed depression-like behavior as we expected.The groups of curcumin antagonist and the fluoxetine were designed in the beginning toevaluate the effect of these two drugs on antidepressant action. The chronic unpredictablemild stress had negative impact on the increase of rats’ weight and their preference of sugar, while the curcumin and fluoxetine improved this negative situation. In the openfield test, the stressed rats showed a prolonged time spent in the center, and a decreasedvelocity and distance moved. The serum cortisol and adrenocorticotropic hormone levelwas obviously increased in stressed rats. All of the results indicated that the stressed ratsshowed depressive-behavioral changes, while curcumin and fluoxetine could significantlyimprove this situation.2. To detect the ultrastructural change in masseter muscles of CUMS rats and toobserve the role of curcumin in this aspect.In this part of the experiment, we produced a control group, CUMS group, high, mediumand low does of curcumin groups and fluoxetine group. We observed the ultrastructure ofthe superficial layer, deep layer of masseter muscles and the gastrocnemius in all6groupsof rats by transmission electron microscopy (TEM). TEM observation indicated that theultrastructural changes occured in stressed rats, mainly in mitochondria and some of theendoplasmic reticulum. Severe mitochondrial swelling and vesiculation and slightexpansion of endoplasmic reticulum was found in both masseter muscles andgastrocnemius of CUMS rats, while high does of curcumin showed a ideal mitochondrialprotective effect.3. To detect the oxidative stress in masseter muscles of CUMS rats and to observe therole of curcumin in this aspect.In this part of the experiment, we tested the activity of SOD, CAT and GSH-Px, thecontent of MDA and the mRNA expression level of Mn-SOD, HSP70, HSF1mRNA andthe protein expression of the HSP70, HSF1both in the superficial layer, deep layer ofmasseter and gastrocnemius muscles. The results showed that the activity of SOD, CAT,and GSH-Px significantly reduced, the MDA content ascended, the expression level ofMn-SOD mRNA decreased while the HSP70、HSF1mRNA and protein increased in boththe superficial layer, deep layer of masseter and gastrocnemius muscles. The resultssuggested that the masseter muscle was in the state of oxidative stress injury. Curcumin could reverse the oxidative stress injury in a dose-dependent way, suggesting thatcurcumin has an effect of improving the level of oxidative stress and maintaininghomeostasis. The superficial and deep parts of masseter and gastrocnemius muscles hadsimilar response to both stress and antidepressant drugs, suggesting that effect of stress onfree radical metabolism was nonspecific.4. To evaluate the energy metabolism in masseter muscles of CUMS rats and toobserve the role of curcumin in this aspect.In this part, we tested the activity of Na+-K+ATPase enzyme, Ca2+-Mg2+ATPaseenzyme and LDH enzyme, the content of LD, and the expression of AMPK, PPAR andUCP3mRNA and protein. The results showed that, both in masseter muscle and thegastrocnemius, the activity of Na+-K+ATPase, Ca2+-Mg2+ATPase and the expression ofAMPK, PPAR, UCP3mRNA and protein decreased significantly, while the activity ofLDH and the content of LD increased. The results indicated that the CUMS can causeabnormal metabolism of masseter muscle, which can be reversed by curcumin in adose-dependent way. It suggested that curcumin could improve the condition of energymetabolism and protect muscle cells. Besides, the reaction of the deep and superficialparts of masseter muscle and gastrocnemius to stress and antidepressant drugs wereconsistent, indicating that the effects of stress on masseter muscle and gastrocnemius wasnonspecific. |
PDF Full Text Request