| Objective: Diabetes (diabetes mellitus, DM) is a metabolic disease, with the people's standard of living and environmental change, the incidence of complications increased year by year. There is now the complications of diabetes research focused on the heart, kidneys, retinal disease mechanism research, but relatively little research on the lungs. High glucose via non-enzymatic protein glycation, polyol pathway activation of diacylglycerol (Diacylglycerol, DAG) - protein kinase C (Protein KinaseC, PKC) pathway and oxidative stress leading channels such as transforming growth factor-β(tran-sforming growth factor -β, TG F-β), mitogen-activated protein kinase (mitogen-activated protein kinase, MAPK) activation, MAPK activation can also increase the impact and interaction of TGF-β1 fibronectin (fibro nectin, FN). PKC in a number of intracellular signaling pathways Center, constitute the cell's critical information network system to participate in many physiological and pathological processes in vivo. DAG-PKC pathway activation in diabetes is an important part of lung injury. TGF-βsignals, such as fibrosis, cancer, cardiovascular and cerebrovascular diseases and other pathological changes of many important diseases, play a pivotal role. TGF-βis a kind of multi-cell regulation of peptides, in mammals there are three kinds of subtypes, respectively, referred to as TGF-β1, TGF-β2, TGF-β3. TGF-β1 has been proven with a number of pulmonary fibrosis (pulmonary fibrosis, PF) disease-related. Activation of TGF-β1 expression allows MAP K activity increased. MAPK pathway is the signal from the cell membrane to the nucleus to pass a primary access, which is promoting cell proliferation and transmission of stress signals a key kinase. The family includes extracellular signal-regulated kinase (extracellular signal-regulated kinase, ERK), c-Jun N-terminal kinase (c-JunN-terminal kinase, JNLK), p38MAPK and other sub-clan, of which the experimental data show that p38MAPK in diabetic lung injury The formation and development plays a very important role. p38MAP K a variety of risk factors for DM common signaling pathway intersection. In this study, intraperitoneal injection of streptozotocin (streptozotocin, STZ) diabetic rat model of the method to copy Observation: 1, diabetic rats widened alveolar septa, pulmonary interstitial increase, and some shrink or even collapse of alveolar cavity; alveolar capillary distorted. 2, detected by immunohistochemistry in lung tissue PKC, TGF-β1, FN expression changes, and average optical density analysis of them; 3, RT-PCR semi-quantitative detection of lung tissue expression of p38 MAPKmRNA. To make it clear diabetic lung tissue PKC, TGF-β1, FN, p38M APK relationship between Of PKC-TGF-β1-p38MAP K signal transduction pathway and FN expression on lung injury in diabetic rats and the mechanisms for diabetes prevention and treatment of lung injury provide a theoretical basis.Method: 1. Experimental group and the diabetic rat model of replication: 60 male SD rats were fed 1 week after adaptation, were randomly divided into normal control group (N) and diabetic model group (DM) group, 30 rats in each group. DM rats by intraperitoneal injection of a one-time 60mg/kgSTZ solution, the normal control group, intraperitoneal injection of citrate buffer equal above. Tail vein blood after 72h fasting blood glucose and qualitative urine sugar, fasting blood glucose≥16.7mmol / L, urine qualitative≥+ + +, animals, polydipsia, increased food and urine were identified as a DM model. During the feeding experiment and control groups were given the same diet and water. Unused during any treatment including insulin, respectively, the first 4 weeks of the experiment, 8 rats were killed over the weekend of 10 drawn.2.Blood glucose and body weight determination: The Johnson & Johnson One TouchⅡ-type blood glucose meter, after 12 hours of fasting, take rat tail peripheral capillary whole blood determination of fasting blood glucose. And use weighing scales body weight, both once a week. 3. Specimens from lung tissue specimens HE staining, light microscope observation of pathological changes in lung tissue.4. Diabetic rats Immunohistochemical analysis of lung tissue: the normal control group and diabetic rats lung tissue biopsies, immunohistochemical staining. To compare different course of lung tissue of rats in each group in PKC, TGFβ-1, FN protein staining the circumstances, Jetta JEDA801D morphological image analysis system software to calculate the average optical density of each specimen, and each group mean comparison between groups .Results: 1.Diabetic rats blood glucose was significantly higher than the same period in the control group, body weight decreased significantly (p <0.01);2. HE stain histologic findings: Diabetic rats widened alveolar septum, pulmonary interstitial increase, and some shrink or even collapse of alveolar cavity; alveolar capillary distortions.3.Immunohistochemistry staining found: lung tissue of diabetic rats PKC protein expression significantly up-regulated, and TGF-β1, FN protein expression in parallel with progressive increase, and gradually increased with the duration of the extension.4.p38MAPK mRNA expression in the diabetic group significantly increased compared with the normal group, statistically significant.Conclution: 1.The model rats were significantly increased blood glucose, body weight decreased significantly, diabetes mellitus model copied successfully.2.Diabetic rats widened alveolar septa, pulmonary interstitial increase, and some shrink or even collapse of alveolar cavity; alveolar capillary distortions. At the same time in rat lung tissue TGF-β1, FN protein expression was increased, confirmed the existence of diabetes, pulmonary fibrosis.3.PKC expression in lung tissue of diabetic rats significantly increased to promote TGF-β1 and its receptor, induced TGF-β1-p38MAPK signal transduction pathway in TGF-β1, p38MAPK expression increased.4.PKC-TGF-β1-p38MAPK signal transduction pathway in TGF-β1, p38MAP K caused an increase in the accumulation of FN, thus contributing to pulmona- ry fibrosis.
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