| Objective: Malignant pleural effusion(MPE) refer to malignancymetastasis to the pleura or pleural primary tumor-induced pleural effusion. Thegeneration of malignant pleural effusion, often marks the disease has enteredthe late and don’t have the chance of operation, generally. The purpose oftreatment is to reduce the generation of pleural effusion, improve the patient’squality of life and try to prolong the survival of patients. At present, thetreatment is often use small-caliber central venous catheter to drain the pleuraleffusion and then apply pleurodesis after pleural injected drugs. Application ofthrombin and talcum powder as pleural adhesions agent treatment of pleuraleffusion for a long time, but the adhesion effect and therapeutic mechanismremains unclear. This study was designed to injected VX2rabbit tissuesuspension (squamous cell carcinoma derived from a tumor induced by theshope virus nipple) to intrathoracic to establish MPE model, given thrombinand talcum powder to treat the MPE, in order to study and explore thethrombin and talcum powder in the treatment of MPE treatment mechanism.Methods: Selected healthy New Zealand white rabbits (8to10months old,male and female equally divided, weighing about3kg) and injected1.5mLVX2tissue suspension to the right pleural, then the rabbit producted pleuraleffusion by B ultrasonic positioning (>10ml), extracted effusion to do cytology,found cancer cells, that proved to be successful for the MPE model. DividedMPE model into four groups: thrombin low-dose group(10), thrombinhigh-dose group(10), talcum powder group(10), the control group(6). Allmalignant pleural effusion models were set small caliber chest drainage andextracted all of the pleural effusion by injection syringe and recorded thedrainage volume. Injected drug into pleural: thrombin low-dose group were given200iu/kg and thrombin high-dose group were given400iu/kg; talcumpowder group were given100iu/kg(10%talcum powder suspension), thecontrol group were given normal saline. On the day of the injection and48hours after injection extracted the pleural effusion to detect hydrothoraxbiochemical detection(including glucose, lactate dehydrogenase) and thechanges of plasminogen activator inhibitor-1(PAI-1), vascular permeabilityfactor(VEGF) by enzyme-linked marker assay(ELISA) and to observe thechanges of volume and colour of chest drainage. During the experiment, thelaboratory animals were implemented unified management and feeding.Opened the pleural cavity after the rabbits died, to observe and record thepleurodesis scores situation of the groups. Take the parietal pleuraorganization to do HE staining by microscope, measuring the thickness of thepleura.Results：1Two of the talcum powder group after injected drugs appear to haveshortness of breath, the nose incitement, and died at a short period of time.The rabbits of thrombin low-dose group(10)，thrombin high-dose group(10)talcum powder group(8) and control group(6) successfully completed theexperiment.2Copy malignant pleural effusion model of the minimum required11days,the longest required23days and the average modeling time was （17.10±2.79）days.3The survival time after pleural injected low-dose thrombin was3.90±0.74days, high-dose thrombin was6.90±1.20days, talcum powder was7.10±1.20days and control group was3.30±0.67days; Between the different groups, thethrombin low-dose group and thrombin high-dose group (P=0.000), thrombinlow-dose group and talcum powder group (P=0.000), the thrombin high-dosegroup and the control group comparison (P=0.000), talcum powder group andthe control group (P=0.000) were significant differences.4The colour of pleural effusion of malignant pleural effusion model couldbecomes bloody and then dark bloody by the short bloody. With the progress of the disease, drainage increased and the color gradually deepened. Thepleural fluid color becomes pale bloody or yellowish after thrombin andtalcum powder treated.5The amount of pleural effusion after pleural injected low-dose thrombin was30.00±12.00ml, high-dose thrombin was28.17±4.40ml, talcum powder was26.00±10.33ml and the control group (49.67±7.53) ml; Between the differentgroups, thrombin high-dose group and control group (P=0.004), talcumpowder group and control group (P=0.006) were significant differences.6The biochemical characteristics of thoracic drainage6.1Glucose (GLU)Relatively the same before and after treatment, thrombin low-dose group(P=0.000), the thrombin high dose group (P=0.005), talcum powder group(P=0.012), and the control group (P=0.001) of glucose than before treatmenthad downward trend and there were significant differences.Glucose content in the different groups before and after treatment, thrombinhigh-dose group and the control group (P=0.007), talcum powder group andthe control group (P=0.003) were significant differences. The inspection levelα=0.0083.6.2Lactate dehydrogenase (LDH)Compared to the same group before and after treatment, thrombin low-dosegroup (P=0.000), the thrombin high-dose group (P=0.0031), talcum powdergroup (P=0.000) and the control group (P=0.000) of LDH than beforetreatment tended to increase and there were significant differences.Different between the two groups before and after treatment, thrombinhigh-dose group and the control group (P=0.006), talcum powder group andthe control group (P=0.004), thrombin low-dose group and talcum powdergroup (P=0.006) were significant differences.7cytokine content of thoracic drainage7.1PAI-1levelCompared the same group before and after treatment, thrombin low-dosegroup (P=0.007), thrombin high-dose group (P=0.008), talcum powder group (P=0.009) of PAI-1higher than that before treatment, have statisticallysignificant.Different between the two groups before and after treatment, thrombinhigh-dose group and the control group (P=0.005), talcum powder group andthe control group (P=0.007) of PAI-1had significant differences.7.2VEGF levelsCompared the same group before and after treatment, the thrombinlow-dose group (P=0.453), the thrombin high-dose group (P=0.388), talcumpowder group (P=0.802) and the control group (P=0.133) in VEGF levels hadno significant difference.The comparison of the thrombin low-dose group, the thrombin high-dosegroup, talcum powder and control groups have no statistically significant(x=1066, df=3, P=0.785).8The comparison of the pleural adhesions integral of thrombin low-dosegroup, the thrombin high-dose group, talcum powder group and the controlgroup had significant difference (P=0.000);The comparison of the pleuraladhesions integral of the thrombin high-dose group and thrombin low-dosegroup (P=0.000), thrombin low-dose group and talcum powder group(P=0.000) had significant difference.9The observation of pleural pathology9.1The findings of microscopeIn control group,the pleura was very thin, inflammatory cells and fibroblastsin connective tissue was obvious; In thrombin low-dose group, pleura isslightly thickened, showing a little inflammatory cell infiltration; In thrombinhigh-dose group, the parietal pleura was significantly thicker and a largenumber of capillaries and fibroblast proliferation and necrosis; In the talcumpowder group, parietal pleura significantly thickened and a large number ofcapillaries and fibroblasts proliferation and surrounding the tumor tissue.9.2pleural thicknessMeasuring the thickness of the parietal pleura at high magnification, thrombinlow-dose group was (0.308±0.016)mm, the thrombin high-dose group was (0.744±0.007)mm, talcum powder group was (1.508±0.043)mm and thecontrol group was (0.107±0.058)mm. Pairwise comparisons were statisticallysignificant (P=0.004).Conclusions:1The method of application VX2tissue suspension to copy the malignantpleural effusion model is simple, require short modeling time and have highforming.2Injected thrombin to thorax could thick of the parietal pleura; also byinhibiting the activity of plasminogen to fibrin deposition; stimulat the pleurafibroblasts increased and accelerat pleural closed;have no significant onreducing VEGF. The method of application of400iu/kg thrombin solution totreat MPE is safe and effective and had no significant side effects.3Injected talcum powder to thorax could mark thickening of the parietalpleura;stimulate the pleural produce reactive inflammation, increase theamount of fibroblasts and accelerate fibrosis; reduce the activity ofplasminogen and the decomposition of fibrous protein, promote pleuraladhesions; have no significant on reducing VEGF. The treatment of10%talcum powder suspension had certainly effect,but also had obvious sideeffects and can cause sudden death of some of the MPE model. |
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