The Experiment Study Of Kidney Injury Related To Chronic Obstructive Pulmonary Disease By Extra-pulmonary Inflammation Effect

Objective: Chronic obstructive pulmonary disease(COPD) is a kind of disease related with reinforced chronic inflammatory reaction between airway and lung to harmful gases or particles like tobacco smoke including local and extra-pulmonary inflammation. Local inflammation effect can cause persistent airflow limitation and developing pulmonary impairment, and extra-pulmonary inflammation can lead to a significant increase in the risk of cardiovascular disease, but whether the extra-pulmonary inflammation effect would also cause kidney injury? In the study, COPD rat model was used to explore effect and relevant mechanism of inflammation effect of COPD on kidney, providing theoretical basis for the clinical early detection and effective prevention and treatment of kidney injury associated with COPD. Methods: Sixteen wistar rats were randomly divided into two groups: COPD model group(group C, n=8) and control group(group N, n=8). The rats in group C were exposed to cigarette smoke twice daily plus intratracheal instillation of lipopolysaccharide(LPS) to establish COPD model. After successful establishment of the COPD model, the clinical manifestations of rats were observed. Urina sanguinis of rats were collected to determine the concentration of urinary microalbumin(m Alb). The concentration of serum cystatin C(Cys C), C-reactive protein(CRP) and tumor necrosis factor-a(TNF-α) in blood serum of the two groups of rats were detected. The contents of CRP, TNF-α in the lung and kidney homogenate were detected by ELISA. The pathological changes of lung and kidney were observed under light microscope with HE staining.The ultrastructural changes of kidney tissue were observed by electron microscope. Results: 1.General condition of rats: The rats in group C experienced a gradual increase in yellow hair, less dark hair, slight weight increase, reduced food intake, slow action. At the late stage of modeling, the rats in group C showed cyanosis of lips and limbs, wheezing, deeply and rapidly breathing and abdominal muscle convulsion. However, the rats in group N showed no above these characteristics. 2.The urinary m Alb concentration(mg/L) of two groups: group C(3.29±0.60) was significantly higher than group N(1.89±0.20)(P<0.01). 3. Serum Cys-C concentration(mg/L) of two groups: there was a significant increase in group C(0.07±0.163) than group N(0.03±0.005)(P<0.01). 4.TNF-α concentration(pg/m L) in serum, lung and kidney homogenate of two groups: TNF-α concentration in serum of group C(251.28±13.83) was obviously higher than group N(202.76±7.24)(P < 0.01). TNF-a concentration in the lung tissue homogenate of group C(244.84±15.10) was obviously higher than that in the N group(21.696±10.45)(P<0.01). TNF-a concentration in renal tissue homogenate of group C(254.9±26.49)was obviously higher than that in group N(206.17±16.78)(P<0.01). 5.CRP content(ng/m L)in serum, lung and kidney tissue homogenate of two groups: CRP content in serum of group C(7.78±0.21) was obviously higher than that in group N(7.269±0.15)(P<0.01). CRP content in the lung tissue homogenate of group C(8.13±0.33) was obviously higher than that in the group N(7.29±0.16)(P<0.01). CRP content in the kidney tissue homogenate of group C(8.03±0.30) was obviously higher than that in group N(7.19±0.49)(P<0.01). 6. Correlation analysis of detection indexes of rats in group C: The m Alb in urine was positively correlated with TNF-α(r=0.949, P<0.01), CRP(r=0.738, P<0.05) in serum, TNF-α(r=0.946, P<0.01), CRP(r=0.906, P<0.01) in lung tissue and TNF-α(r=0.902, P<0.01), CRP(r=0.933, P<0.01) in kidney tissues. The serum Cys C concentration was positively correlated with TNF-α(r=0.944, P<0.01), CRP(r=0.832, P<0.05)in serum, TNF-α(r=0.918, P<0.01), CRP(r=0.979, P<0.01)in lung tissues, and TNF-α(r=0.981, P<0.01), CRP(r=0.936, P<0.01) in kidney tissues. TNF-α in kidney and lung tissues showed a positive correlations(r=0.879, P<0.01). CRP in kidney and lung tissues showed positive correlations(r=0.859, P<0.01). 7.The pathological changes of lung tissues: compared with group N, group C showed bronchial lumen stenosis, smooth muscle hyperplasia, part of the degeneration and necrosis of bronchial epithelial cells, increase of goblet cells, infiltration of inflammatory cells in the lung tissue, alveolar wall damage, expansion of the alveolar space, formation of the bullae of lung, thickening of alveolar septum. Mean inner lining interval(MLI) in group C(88.5±23.10) were obviously higher than that in group N(48.4±6.87)(P<0.01). Alveolar damage index(DI) of group C(59.9±9.87)were significantly higher than group N(22.1±5.94)(P<0.01). 8.The pathological changed in renal tissue: compared with group N, group C showed visible hyperemia and expansion in glomeruli, renal tubular epithelial cell swelling. 9. The ultrastructure of renal tissue: the renal tissue of rats in group C showed the fusion of glomerular foot process, endoplasmic reticulum expansion, mitochondrial swelling, and focal degeneration of renal tubular epithelial cell. However, the renal tissue of rats in group N showed no above these changes. Conclusion: 1. COPD rat model can be successfully reproduced by exposure to cigarette smoking plus intratracheal instillation of lipopolysaccharide. 2. In the development of COPD, it can cause a certain degree of renal injury. 3. Renal injury resulted from COPD was closely related to extra-pulmonary inflammation effect, which might be one of the mechanisms of renal injury associated with COPD.