Humans ; Lung Neoplasms ; diagnosis ; therapy ; Mesothelioma ; diagnosis ; therapy ; MicroRNAs

OBJECTIVETo compare the effects of oral treatment with tetrandrine (TD) and N-acetylcys-teine (NAC) separately or jointly on silica-exposed rats.

METHODS40 sprague-Dawly (SD) rats were randomly divided into normal saline group, quartz group, TD treatment group (50 mg/kg), NAC treatment group (500 mg/kg) and combined treatment group (TD: 50 mg/kg + NAC: 500 mg/kg). Rats in normal saline group and other groups received intratracheal instillation of normal saline and quartz dust suspension respectively. Treatment groups were given TD, NAC separately or jointly via esophagus the next day after instillation, once a day and six times a week for 30 consecutive days. At the end of experiment, the pathological changes of lung tissues were evaluated by the methods of Foot, HE and Masson staining, the level of hydroxyproline (HYP), malondjalde-hyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lung tissues were measured by alkaline hydrolysis method, the barbituric acid method and enzyme-linked immunosorbent assay (ELISA) respectively.

RESULTSCompared with the quartz group, lymph nodes/body coefficients in all treatment groups and lung/body coefficient in combined treatment group were significantly decreased (P < 0.05). Pathology results showed that the normal saline group demonstrated no obvious evidence of lung damage. The quartz group lungs silicotic lesions focused on II~III level, the TD treatment group was mainly with I level, the NAC treatment group was mainly with I~II level, and the combined treatment group only showed little silicotic nodule, no obvious fibrosis. HYP content in TD treatment group and combined treatment group were significantly lower than that in the quartz group (P < 0.05), while it showed no obvious change in NAC treatment group. MDA content in lung tissues of each treatment group (TD treatment group, NAC treatment group and combined treatment group) were 18.80 ± 2.94, 20.13 ± 4.01 and 17.05 ± 3.52 nmol/ml respectively, which lower than in the quartz group (23.99 ± 3.26 nmol/ml). The level of IL-6 in lung tissues of the quartz group were 89.57 ± 8.78 pg/ml. After TD and NAC monotherapy, the IL-6 content decreased to 79.22 ± 9.65 pg/ml and 81.63 ± 5.72 pg/ml, and it decreased more significantly after combined medication (74.37 ± 3.17 pg/ml). The level of TNF-α in the quartz group were 59.05 ± 4.48 pg/ml. After TD and NAC monotherapy, the TNF-α content decreased to 50.48 ± 2.76 pg/ml and 54.28 ± 4.30 pg/ml, and it decreased more significantly after combined medication (49.10 ± 4.98 pg/ml).

CONCLUSIONNAC and TD could reduce MDA, TNF-α and IL-6 levels in lung tissue, and alleviate SiO2-induced pulmonary fibrosis in rats. Combined treatment with TD and NAC was more effective than TD or NAC treatment separately.

Acetylcysteine ; pharmacology ; Animals ; Benzylisoquinolines ; pharmacology ; Disease Models, Animal ; Dust ; Hydroxyproline ; metabolism ; Interleukin-6 ; metabolism ; Lung ; pathology ; Malondialdehyde ; metabolism ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; Quartz ; toxicity ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Silicosis ; drug therapy ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVE To investigate the potential mechanism of procyanidin on rats with gingivitis by regulating phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/vascular endothelial growth factor （VEGF） signaling pathway. METHODS The rat model of gingivitis was constructed by sewing the neck of the first maxillary molar with silk thread+applying maltose on the gum+feeding with 20% sucrose solution and soft food. Forth-eight model rats were randomly divided into model group， procyanidin group （160 mg/kg）， 740Y-P group （PI3K/Akt signaling pathway activator， 0.02 mg/kg）， and procyanidin+ 740Y-P group （procyanidin 160 mg/kg+740Y-P 0.02 mg/kg）， with 12 rats in each group； another 12 rats were selected as control group； each medication group was treated with corresponding drugs intragastrically or/and intraperitoneally， once a day， for 7 consecutive days. Twenty-four hours after the last administration， the gingival index of rats was measured； the levels of interleukin- 18 （IL-18）， inducible nitric oxide synthase （iNOS） and alkaline phosphatase （ALP） in gingival crevicular fluid， as well as the levels of superoxide dismutase （SOD）， catalase （CAT） and reactive oxygen species （ROS） in gingival tissues of rats were detected； the pathological changes in gingival tissues were observed； the expression levels of PI3K/Akt/VEGF signaling pathway- related proteins in gingival tissues of rats were detected. RESULTS Compared with control group， the gingival tissues of rats in the model group had severe pathological damage，which was manifested as local tissue expansion and congestion， new capillaries， degeneration and loss of collagen fibers and disorder of arrangement， and a large number of inflammatory cell infiltration in the gingival sulcus wall. The gingival index， the levels of IL-18， iNOS， ALP in gingival crevicular fluid， the level of ROS in gingival tissues， the phosphorylations of PI3K and Akt， as well as the protein expression of VEGF in gingival tissues were significantly increased； the levels of SOD and CAT in gingival tissues of rats in model group were significantly decreased （P＜0.05）. Compared with model group， the pathological damage to the gingival tissues of rats in procyanidin group was reduced， and all quantitative indicators were significantly improved （P＜0.05）； 740Y-P could reverse the improvement effect of procyanidin on various indicators （P＜0.05）. CONCLUSIONS Procyanidin may alleviate gingival tissue damage， and improve gingival inflammation and oxidative stress in rats with gingivitis by inhibiting PI3K/Akt/VEGF signaling pathway.