| Objective: To study the effect of experimental pleurodesis in rats induced by different dose of silver nitrate and talc, and the role of transforming growth factorβ1(TGF-β1) in the mechanisms of pleurodesis. To find a better sclerosing agent for clinical treatment.Methods: Adult Sprague-Dawley rats 150 underwent pleurodesis as follows: 6 rats received 1ml 0.9% Sodium Chloride solution as control group; Six groups called as T1, T2, T3, A1, A2, A3, that of 24 rats were injected into thoracic cavity as follow: talc, 500 mg/kg ,100 mg/kg or 50 mg/kg, and silver nitrate, 0.05%, 0.1% or 0.5%. Six rats in each group were killed at 1d, 1w, 2w, and 4w (control group at 1d ) after intrapleural injection. Samples of blood, pleural fluid and right lung tissue were collected. Eukocytes was assayed. Observed the degree of gross pleurodesis, the amount of microscopic pleural fibrosis and inflammation were graded on a scale of 0 to 4. Pleural fluid volume at the first 24 hours, and TGF-β1 expression in the integral optical density in lung tissue.Results:1. The groups of talc:1.1 Pleural adhesion scores: In all groups pleurodesis score expressed better as time goes on. At the week4 each group reached the maximum adhesion points. The average pleurodesis score of rats in group: talc 500mg/kg 2.33±0.77, talc 100mg/kg 1.83±0.75, talc 50mg/kg 1.33±0.52. Talc 500mg/kg was significant higher than talc 50mg/kg at the week4 (P<0.05).1.2 Pleural inflammatory reaction scores: The microscopic pleural inflammation grades expression were positive for each observation time in three groups. They began to increase at the day1 and peak at the week1, and then decreased gradually to the day1 level at the week4. At the week1, the average pleural inflammatory reaction scores of rats in group: talc 500mg/kg 2.83±1.17, talc 100mg/kg 2.50±1.05, talc 50mg/kg 2.00±1.10, there was no significant different from each other (P>0.05).1.3 Pleural fibrosis scores: The pleural fibrosis began to increase at the day1 and peak at the week2, and then decreased gradually. At the week2, the average pleural fibrosis scores of rats in three groups: talc 500mg/kg 2.67±0.82, talc 100mg/kg 2.00±0.89, talc 50mg/kg 1.33±1.07. Talc 500mg/kg was significant higher than talc 50mg/kg (P<0.05).1.4 Blood levels of WBC: At the day1, blood levels of WBC in rats received different doses of talc were significant higher than control group (P<0.05). Talc 500mg/kg was greater than talc 100mg/kg and 50mg/kg (P<0.05). The level of WBC at the week1 was greater than at the day1 in the three groups. Talc 500mg/kg was greater than talc 50mg/kg at the week1 (P<0.05).1.5 Pleural fluid volume at 24h: The pleural fluid volume at 24h in the rats received talc 500mg/kg was 1.88±0.78, which was significant higher than the volume of 1.03±0.59 and 0.60±0.32 in the rats that received talc 100mg/kg and 50mg/kg(P<0.05).1.6 Lung levels of TGF-β1: There was no significant difference between control group and groups received three different dose of talc (P>0.05). The Lung levels of TGF-β1 peak at week2, and significant higher than at the day1 and week4 in rats that received talc. At the week2, the average TGF-β1 scores of rats in three groups: talc 500mg/kg 6.17±1.60, talc 100mg/kg 4.00±1.26, talc 50mg/kg 3.33±1.63. Talc 500mg/kg was significant higher than talc 50mg/kg (P<0.05).1.7 The general state: There were some differences after operation. Spirit was somewhat less in the rats that received talc 100mg/kg and 50mg/kg at the first day, and can eat a small amount of food. The second day they restored. Rats received talc 500mg/kg at the first day showed poor spirit and only drank a little of water. The next day they had a slight recovery. The third day, there was no difference with groups of talc 100mg/kg and 50mg/kg. There was no death after operation. 2. The groups of silver nitrate:2.1 Pleural adhesion scores: In all groups pleurodesis score expressed better as time goes on. At the week4 each group reached the maximum adhesion points. The average pleurodesis score of rats in three groups: silver nitrate 0.5% 3.50±0.55, silver nitrate 0.1% 3.17±0.75, silver nitrate 0.05% 1.67±0.52. Silver nitrate 0.5% and 0.1% were significant higher than silver nitrate 0.05% at the week4 (P<0.05).2.2 Pleural inflammatory reaction scores: The expression of pleural inflammation grades was positive at each of the observation times in three groups. They began to increase at the day1 and peak at the week1, and then decreased gradually to the day1 level at the week4. At the week1, the average pleural inflammatory reaction scores of rats in three groups: silver nitrate 0.5% 3.67±0.52, silver nitrate 0.1% 3.33±0.82, silver nitrate 0.05% 2.33±1.03. Silver nitrate 0.5% was significant higher than silver nitrate 0.05% at the week1, week2 and week4 (P<0.05).2.3 Pleural fibrosis scores: The pleural fibrosis expression was positive at each of the observation times in three groups, and began to increase at the day1 and peak at the week4. At the day1, there was no significant difference in rats which were used different dose of silver nitrate. At the week1, the average pleural fibrosis scores of rats in three groups: silver nitrate 0.5% 3.00±0.89, silver nitrate 0.1% 2.67±0.81, silver nitrate 0.05% 1.17±0.85. There was no significant difference between silver nitrate 0.5% and 0.1% (P>0.05), but they were both greater than silver nitrate 0.05% (P<0.05). The mean±SEM gross pleural fibrosis score in the rats that received silver nitrate 0.5% was 3.50±0.84, which was significantly higher than the score of 1.83±0.75 in the rats that received silver nitrate 0.05% at the week2. At the week4, silver nitrate 0.5% 3.67±0.52, silver nitrate 0.1% 3.33±0.52, silver nitrate 0.05% 2.17±1.17, silver nitrate 0.5% and 0.1% were significant higher than 0.05%(P<0.05).2.4 Blood levels of WBC: At the day1, the blood levels of WBC in the rats that received different doses of silver nitrate were significant higher than control group (P<0.05). Silver nitrate 0.5% and 0.1% were significant higher than silver nitrate 0.05% (P<0.05). The WBC level at the week1 was greater than at the day1 in the rats that received three different dose of silver nitrate. Silver nitrate 0.5% was greater than silver nitrate 0.05% at the week1 (P<0.05). There was no significant difference between silver nitrate 0.5% and 0.1% at the two observation time (P>0.05).2.5 Pleural fluid volume at 24h: The pleural fluid volume at 24h in the rats that received silver nitrate 0.5% was 4.37±1.00, which was significant higher than the volume of 2.20±0.65 and 0.77±0.20 in the rats that received silver nitrate 0.1% and 0.05%(P<0.05). Silver nitrate 0.1% was significant higher than silver nitrate 0.05% (P<0.05).2.6 Lung levels of TGF-β1: Silver nitrate 0.5% was greater than control at the day1 (P<0.05). In all groups TGF-β1 expressed better as time goes on. The expression of TGF-β1 at the week1 and week2 were significant higher than at the day1 and week4 in the rats received silver nitrate 0.5% and 0.1%(P<0.05). Silver nitrate 0.5% was greater than silver nitrate 0.05% at the week1. Silver nitrate 0.5% and 0.1% were greater than silver nitrate 0.05% at the week2 (P<0.05). There was no significant difference at each of the observation times in the rats that received silver nitrate 0.5% and 0.1% (P>0.05).2.7 The general state: The spirit showed somewhat less in the rats that received silver nitrate 0.05% at the first day, and the rats can eat a small amount of food. They restored at the second day. Rats received silver nitrate 0.1% at the first day showed poor spirit, only drank a little of water. The next day, they had a slight recovery. At the third day, there was no difference with the rats that received silver nitrate 0.05%. However, there were 4 died in the group that received silver nitrate 0.5%, for the rest showed bad spirit, with mouth and nose bleeding, no drink and no food. The second day 2 died, the survivors still showed poor spirit, but could drank a little of water, no bleeding at their mouths and noses. The spirit and diet had a slight recovery at the third day. After a gradual recovery, there was no difference with other groups at the fifth. 3 Comparison between talc and silver nitrate:3.1 Pleural adhesion scores: Silver nitrate 0.5% was significant greater than talc 500mg/kg at the week2. Silver nitrate 0.5% and 0.1% were significant greater than talc 500mg/kg at week4 (P<0.05).3.2 Pleural inflammatory reaction scores: There was no significant difference among silver nitrate 0.5%, 0.1% and talc 500mg/kg at each of the observation times(P>0.05). Silver nitrate 0.5% was significant greater than talc 100mg/kg and 50mg/kg at the week1, week2 and week4 (P<0.05). Silver nitrate 0.1% was significant greater than talc 50mg/kg at the week1 and week2 (P<0.05).3.3 Pleural fibrosis scores: There was no significant difference between silver nitrate and talc at the day1. At the week1 and week2, there was no significant difference among silver nitrate 0.5%, 0.1% and talc 500mg/kg(P>0.05), but silver nitrate 0.5% was significant higher than talc 100mg/kg and 50mg/kg at the week2(P<0.05). Silver nitrate 0.5% and 0.1% were significant greater than talc at the week4 (P<0.05).3.4 Blood levels of WBC: There was no significant difference among silver nitrate 0.5%, 0.1% and talc 500mg/kg at the day1 and week1 (P>0.05).3.5 Pleural fluid volume at 24h: Silver nitrate 0.5% was significant higher than talc (P<0.05). There was no difference between silver nitrate 0.1% and talc 500mg/kg (P>0.05).3.6 Lung levels of TGF-β1: There was no significant difference among silver nitrate 0.5%, 0.1% and talc 500mg/kg at each of the observation times(P>0.05). Silver nitrate 0.5% was greater than talc 100mg/kg and 50mg/kg at the week1 and week2 (P<0.05).3.7 The general state: The postoperative death was 25% in rats received silver 0.5%, and the recovery time was longer than other groups (about 5days). Rats received silver nitrate 0.1% and talc 500mg/kg recovery time was about 3 days, and postoperative death was 0.Conclusion: The effect of pleurodesis produced by talc and silver nitrate is dose-related, the more dose, the more degree of lung injury and causing more degree of pleural adhesions. The main mechanism of pleurodesis is aseptic inflammation and the adhesion process of phlegmonosis cells. TGF-β1 plays an important role in the pleura adhesion process of talc and silver nitrate. Compare the effect of pleurodesis, silver nitrate 0.5% and 0.1% are greater than talc 500mg/kg. But the death rate of silver nitrate 0.5% is greater than silver nitrate. Considering all factors, silver nitrate 0.1% has the valuable of clinical treatment.
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