The Preliminary Study Of Respiratory Dysfunction In Diet-induced Obesity Impuberism Female Rat

Objective:Measure the the role and mechanism of diaphragmatic injury in diet-induced obesity impuberism female Sprague-Dawley rats. To investigate the mechanism of respiratory function in diet-induced obesity impuberism female Sprague-Dawley rats.Methods:30female Sprague-Dawley weaning rats were randomly divided into control group and high-fat diet group according to their body weight.15rats were fed with basic diet and15rats were fed with high-fat diet. At the end of8th week,7obese rats were selected by body weight from high-fat diet group as obese group with leptin resistance, body weight, blood serum leptin concentration. Rats were operated on the8th week. The rats were anesthetized by20%urethane (5ml/kg, ip), then parameters of respiratory function:tidal volume, pulmonary ventilation, forced vital capacity, maximal midexpiratary flow curve, peak inspiratory flow and peak expiratory flow of both group rats were detected. The artery blood gas analysis including partial pressure of carbon dioxide (PaCO2), power of hydrogen partial pressure of oxygen (PaO2), power of hydrogen (pH),oxygen saturation (SaO2) were also recorded. In perfusion diaphragm strips model in vitro, the parameters which reflex the diaphragm contractility including peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT), maximal rates of contraction (+DT/dtmax), maximal rates of relaxation (-DT/dtmax), force-frequency curve and fatigue index (FI) were assessed by Medlab-U/4C biological signal collecting system. The activitives of superoxide dismutase (SOD), succinic dehydrogenase (SDH) and content of malondiadehyde (MDA) and myeloperoxidase (MPO) in diaphragm were detected and the contents of SERCA, titin, nebulin mRNA were detected by reverse transcriptase polymerize chain reactive. The changes of morphology and ultrastructure of diaphragm were studied by light microscopy and electron microscopy in liver cirrhosis rats.Result:The results indicated that:1. Body weight, blood serum leptin concentration, pulmonary ventilation, peak inspiratory flow and peak expiratory flow of obese group were higher than those of control group(P<0.05). No significant difference of tidal volume, forced vital capacity and maximal midexpiratary flow curve were found between both groups.2. Compared with control group, pH、 PaCO2and SaO2in model group had no significant deviation (P>0.05), but PaO2i n model group was significantly decreased (p<0.01).3. Compared with the rats in control group, in model group, Pt, Po, FI were lower (P＜0.01)4. Compared with the rats in control group, in model group, tetanic force under the stimulus frequency of10,20,40,60,100Hz were decreased (P<0.01);5. Electron microscope morphometry of diaphragm in Model group revealed the distribution of the diaphragm can be seen a large number of lipid droplets; muscle fiber edema, a small number of filaments disorder,the quantity of mitochondria was decreased, mitochondria was oedema and expanded, its cristae broken and vague, a great quantity of mitochondria were vacuolization or vesiculation, myelin figures could be seen.6. The activities of SOD, SDH in model group were lower than those in CON group (p <0.01) and the contents of MDA, MPO were increased (P<0.01);7. The expression of SERCA, titin, nebulin mRNA in diaphragm was lower in LC group than those in control group (P<0.01); Conclusions:Obesity with leptin resistance induced by high-fat diet impairs pulmonary ventilation function of female rats. In diet-induced obesity Sprague-Dawley rat, the contractile function of diaphragm had decreased and likely to fatigue. The mechanism may be related to fat deposits in diaphragm and breakage of mitochondria. The mechanisms can be related to these: model could inhibit the activity of antioxidase, induce diaphragm to produce more free radicals, elevate lipid peroxidation level, make mitochondrial dysfunction, inhibit mitochondial related enzymes, raise inflammatory reaction and destroy the diaphragmatic ultrastructure. It could also decrease serca, titin, nebulin mRNA contents.