| The incidence of renal cancer rates second in the urinary system neoplasm, and accounts for 80%-90% of renal malignancies in adults. Renal cancer originates from the epithelia of proximal tubules. Smoking is the main cause of renal cancer, and at least 39% of cases in male are related with it. Cadmium is the major deleterious component in the cigarette and meantime the major pollutant in the environment. The kidneys are the organs impaired most by chronic low-dosage cadmium exposure. Long-term and low-dosage cadmium exposure may impair the epithelia of proximal tubules, resulting in the decreased reabsorption function of proximal tubules. This experiment explored the effect of smoking-dosage cadmium on renal morphology and function.Objective: to observe the influence of smoking-dosage cadmium on renal morphology and function in rats, and explore the effect of smoking-dosage cadmium on the kidneys and the possible mechanism.Method: built the animal model of smoking-dosage cadmium; tested the content of cadmium, copper, calcium and zinc in the kidneys with ICP-MS; tested the BUN and Crea content in the serum and urine, as well as the content of potassium, sodium, calcium and chlorine ions in the serum with ROCHE COBAS 400 full-automatic biochemistry analyzer; sliced the tissue and observed the morphologic change under the optic microscope; examined the expression of MT, PCNA, AQP-1, AQP-2 and AQP-3 with immunohistochemical method; measured the water permeability coefficient of cadmium ion to AQP-1 with the water permeability test method; and inspected the protein expression of AQP-1 in the medullary tissue of the kidneys with Western blot.Results: in the animal model of smoking-dosage cadmium, the coefficients of organs in rats were lower than those of control group(P<0.05)at the 20th week. Compared with the control group, contents of renal cadmium in the model group at various time had significant difference, and cadmium was negatively related with calcium and copper; the serum BUN and Crea had difference at the 36th week compared with the control group; the urine Crea had difference at the 36th, 44th and 52nd week compared with the control group. It was observed under the optic microscope that the tissue structure of renal tubule was impaired in the early phase of the model group, and atypical hyperplasia was observed in the later phase. MTs induced by smoking-dosage cadmium were located in the glomerulus, the outer medullar and proximal tubules in the inner medullar, and expressed in the cell plasma. MTs showed significant difference between the two groups, MTs expression was strongest in the treatment group at the 20th week, and attenuated with the model time prolonging, and it was still higher than the control group at the 52nd week. In the expression of PCNA in the mesangial cells and tubule cells, the positive cell number showed the trend of decreasing first and then increasing, indicating that the smoking-dosage cadmium interfered with the normal synthesis of DNA. Protein expression of AQP-1, AQP-2 and AQP-3 in the kidneys of the smoking-dosage cadmium group decreased, but restored to some extent with the model time prolonging. Protein expression of AQP-1 in the vasa recta had significant difference, attenuated with the model time prolonging and dropped to the lowest at the 52nd week compared with the control group. Cadmium didn't exert"door control"effect to the water permeability of red cells. Protein expression of AQP-1 tested with Western blot in the outer medullar of the kidneys in the model group decreased.Conclusions:1. The animal model of smoking-dosage cadmium was built, contents of renal cadmium in the model group at various time had significant difference compared with the control group, and cadmium was negatively related with calcium and copper.2. the coefficients of organs in model rats were lower than those of the control group with significant difference at the 20th week , the serum BUN and Crea had difference at the 36th week compared with the control group; the urine Crea had difference at the 36th, 44th and 52nd week compared with the control group.3. It was observed under the optic microscope that the tissue structure of renal tubule was impaired in the early phase of the model group, and that could be the pathological basis of renal cancer.In the expression of PCNA in the mesangial cells and tubule cells, indicating DNA was impaired in the early stage and repaired gradually, ultimately resulting in hyperplasia.4. MTs showed significant difference between the two groups, MTs expression was strongest in the treatment group at the 20th week, and attenuated with the model time prolonging, and it was still higher than the control group at the 52nd week. That indicated that the MT induced by cadmium lasted for some time.5. Protein expression of AQP-1, AQP-2 and AQP-3 in the kidneys of the smoking-dosage cadmium group decreased, effect of the reabsorption of the water.In conclusion, smoking-dosage cadmium exerted some effect on renal morphology and function, and its damage to the kidneys lasted for a long time. Thus, the research provides scientific theory and experiment foundation in advising people to give up smoking or to avoid Cadmium intake in the smoking population.
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