Effects of Celastrol on Accelerated Healing of Skin Wounds of Diabetic Ulceration in Rats and Mechanism Revealed by Nuclear Magnetic Resonance-based Metabonomics / 分析化学

The experimental SD rats were randomly divided into normal control group (Con group),diabetic ulcer model group (DM group) and Celastrol group (Cel group).Except the control group,diabetic ulceration rat models were established by intraperitoneal injection of streptozotocin along with skin scald.And then,each group was treated by spraying the saline solution on the affected skin with (Cel group) or without (Con group and DM group) Cel (q.d.×14 d).Nuclear magnetic resonance (NMR)-based metabonomic analysis was applied to detect metabolic characteristics,accompanied by healing rate calculation and HE and Masson staining to study therapeutic effect of celastrol on accelerated healing of skin wounds of diabetic ulceration rats,which could be used to elucidate therapeutic effects of celastrol on the rat diabetic ulceration and its mechanism.The results showed that celastrol could induce epithelial regeneration of the rat ulcer wound,regulate the infiltration of inflammatory cells and the distribution of collagen fibers,and promote the healing of the ulcer wound.About 20 endogenous potential differential metabolites were screened and identified by partial least square analysis.Metabolic pathway analysis was carried out to show that celastrol can significantly recovery the level of the tricarboxylic acid cycle,promote its energy supply,accelerate the protein synthesis,improve mitochondrial dysfunction and oxidative stress,and accelerate the self-repair ability of skin tissue.Celastrol can promote the healing of ulcers skins of the diabetic rats,which contribute to experimental basis of the drugs for the treatment of diabetic ulcers.

Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium / 生理学报

One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium.

Calpain mediates cardiac troponin I degradation in tail-suspended rats / 生理学报

The aim of the present study was to investigate the expressions of calpain and calpastatin in the myocardium of simulated weightlessness rats, and to elucidate the underlying mechanism of cardiac troponin I (cTnI) degradations. Tail-suspended (SUS) rats were used as a simulated weightlessness model on the ground. The myocardium of rats was homogenized, and the expressions of calpain-1, calpain-2, calpastatin and cTnI were analyzed by Western blotting technique. Calpastatin expression was significantly decreased in 2- and 4-week SUS groups compared with that in the synchronous controls (P<0.05). Calpain-2 expression was slightly decreased, whereas calpain-1 expression was unaltered in SUS groups. However, calpain-1/calpastatin and calpain-2/calpastatin ratios were increased after tail-suspension, being significantly higher in 2- and 4-week SUS groups than those in the synchronous controls (P<0.05, P<0.01). Cardiac TnI degradation was significantly increased after tail-suspension (P<0.01), but cTnI degradation in both SUS and control groups was significantly inhibited by a non-specific inhibitor of calpain, PD150606 (P<0.01). These results suggest that an increase in calpain activity may enhance cTnI degradation in the myocardium of tail-suspended rats.