Experimental Study On The Mechanic Impact Of Salidroside On The Lung Tissue MMPs Changes In Acute Paraquat Poisoned Rats

ObjectiveThrough the establishment of an animal model of acute lung injury in paraquat poisoned rats, it can be observed that the effects of salidroside (SDS) on MMP-2, TIMP-1of lung tissue in lung injured acute paraquat (PQ) poisoned rats, aiming to clarify the presence of salidroside’s protective and anti-fibrosis function on lungs.Methods130adult male SD rats were randomly divided into:normal group (NS group,10); PQ model group (60were randomly divided into six subgroups, each10at1d,3d,7d,14d,21d,28d); SDS intervention group (60were randomly divided into six subgroups, each10at1d,3d,7d,14d,21d,28d). Among which, the normal control group is gavaged with1mL saline once, the PQ model group and the SDS intervention group were gavaged with the20mg/kg PQ diluted with1mL saline.Aafter paraquat poisoning1h, the SDS intervention group, was given daily intraperitoneal injection of10mg/kg Salidroside every12hs. As for the NS control group and the PQ model group, they were injected with saline with equal volumn to the SDS group, once every12hs. The PQ model group and the SDS intervention group were taken specimens from the right lower lung tissue under anesthesia anatomical, after paraquat poisoning1d,3ds,7ds,14ds,21ds,28ds. Part of the specimens was stored in refrigerator at-70℃for RT-PCR and Real-time PCR testing, and the other part was rinsed in saline, fixed in10%formalin, dehydrated, made transparent, dipped into wax. And the paraffin-embedded tissue blocks and the. slices, are for HE staining and immunohistochemical staining.ResultsCompared with the normal group, the rats in the PQ model group and the SDS intervention group got the early symptoms of acute lung inflammation, pulmonary edema and obvious bleeding. Changes in pulmonary fibrosis were observed after exposure to PQ for7 days and it came to the climax at28th day; the SDS group got the similar symptoms, but which are relatively mild. In contrast, in the PQ group, the MMP-2protein and mRNA are obviously and increasingly expressed in the lung tissue of rats from on the first day and till the7th day it reached a peak, though declined slowly, still significantly higher than the normal group at the28th day; And the TIMP-1protein expression also significantly enhanced from1st d, reaching a peak at the14th day, then remained high afterwards (P<0.01). Compared with the previous groups, the SDS intervention group kept a significantly lower level at MMP-2and TIMP-1protein and mRNA expression (P<0.05).Conclusion1,20mg/kg paraquat gavage can successfully make animal models of acute lung injury;2, MMP-2, TIMP-1in acute lung injury induced by paraquat poisoning and pulmonary fibrosis plays an important role;3, Salidroside (SDS) can inhibit MMP-2, TIMP-1mRNA expression and protein expression, and restore the balance between the previous two, thus delaying or even inhibiting the fibrotic process.