[Meta-analysis of Ac-SDKP inhibition of Pulmonary fibrosis in animal models].

Objective: To systematically study the anti-fibrotic effect of N-acetyl-seryl-as partyl-lysyl-proline (Ac-SDKP) on pulmonary fibrosis. Methods: In May 2021, a computer search was performed on CNKI, Wanfang Knowledge Service Platform, VIP.com, China Biomedical Literature Database, Pubmed, OVID and other databases. The retrieval time was from January 2008 to May 2021. Randomized controlled experiments on the inhibition of pulmonary fibrosis by Ac-SDKP were screened. The control group was the pulmonary fibrosis model group and the experimental group was the Ac-SDKP treatment group. The quality of the literature was assessed using the syrcle risk of bias assessment tool, and data were extracted. Data analysis was Performed using revman 5.4 software. Results: 18 papers were included, with a total of 428 animal models. The results of meta analysis showed that the contents of α-smooth muscle actin (α-SMA), type I collagen, type Ⅲ collagen, transforming growth factor-ß (TGF-ß) and Nodule area in the exPerimental group were lower than those in the control grouP. [SMD=-2.44, 95%CI (-3.71--1.17), P=0.000][SMD=-5.36, 95%CI (-7.13--3.59), P=0.000] [SMD=-3.07, 95%CI (-4.13--2.02), P<0.000][SMD=-2.88, 95%CI (-3.63--2.14), P=0.000] [SMD=-1.80, 95%CI (-2.42--1.18), P=0.000], the content of hydroxy proline in the experimental group was higher than that in the control group [SMD=7.62, 95%CI (4.90-10.33), P=0.000], all indexes included in the literature were statistically significant. Conclusion: Ac-SDKP has obvious inhibitory effect on the process of pulmonary fibrosis, and may become a new clinical drug for the treatment of pulmonary fibrosis.

[Regulatory effect of Ac-SDKP on phosphorylated heat shock protein 27/SNAI1 pathway in silicotic rats].

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 µg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 µg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 µg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.

Improved systolic function of rat cardiocytes during heart failure by overexpression of SERCA2a.

OBJECTIVE: This study shows that overexpression of SERCA2a can improve the systolic function and reduce the occurr-ence of arrhythmias in cardiocytes isolated from the heart of a rat model of heart failure. MATERIALS AND METHODS: An animal model of rats experiencing heart failure was established by a surgical procedure producing abdominal aortic coarctation. Cardiocytes from sacrificed rats were isolated by a collagenase digestion method. The SERCA2a adenovirus vector was transfected into the cells after 48h of culture. Overexpression of SERCA2a in cardiocytes was verified by Western Blot. Measurements were taken using a single cell dynamic edge detection system to evaluate the effects on the myocardiocyte function and calcium homeostasis. RESULTS: Cardiocytes overexpressing SERCA2a displayed a stronger systolic function and lower occurrence rate of abnormal systolic rhythm than mock-transfected cardiocytes. The contraction rhythm abnormality rate percentage was 5.270 ± 1.566% vs. 3.955 ± 1.684% (p < 0.01). The time at which they reached the maximum contraction (TTP) was 0.095 ± 0.009s vs. 0.114 ± 0.008s (p < 0.01). The time at which they reached 50% of the diastolic amplitude (R50) was 0.039 ± 0.008s vs. 0.057 ± 0.010s (p < 0.01). Finally, the occurrence rate of abnormal systolic rhythm during maximal contraction was 58% vs. 81% (p < 0.01). These results show that all data were significantly improved in the SERCA2a overexpressing group, and that parameters achieved were similar to those in the sham-operated non-heart failure group. CONCLUSIONS: The overexpression of SERCA2a in cardiocytes during heart failure significantly improves cell function and arrhythmia occurrence.

[Decrease of calcitonin gene-related peptide release from mesenteric arterial bed in diabetic rats and effect of nitric oxide].

Our previous work has shown that endotoxin triggers the release of calcitonin gene-related peptide (CGRP) from the mesenteric arterial bed, which is partially mediated by nitric oxide. In the present study, the changes of endotoxin-induced CGRP release from the isolated mesenteric arterial bed and the CGRP mRNA levels in dorsal root ganglia (DRG) of diabetic rats were studied in relation to the effect of nitric oxide. CGRP level in perfusate and the steady-state level of mRNA for CGRP in DRG were determined by RIA and semi-quantitatively by RT-PCR. The results showed that endotoxin (1-25 micrograms/ml) accumulated in perfusate caused concentration-dependent release of CGRP, which was significantly decreased in mesenteric arterial bed of diabetic rats. As compared with age-related control, the endotoxin (10 and 25 micrograms/ml) -induced CGRP release in diabetic rats was attenuated by 27% and 40%, respectively. L-NAME, an inhibitor of nitric oxide synthase, inhibited the effect of endotoxin in dose of 10 and 25 micrograms/ml by 23% and 46%, respectively against the control rats. However, there was no inhibitory effect of L-NAME on endotoxin-induced CGRP release in diabetic rats. The CGRP mRNA level in DRG showed no significant difference between the two groups. These results indicate that the response of the isolated mesenteric arterial bed to endotoxin-induced CGRP release in diabetic rats is significantly lower than that in control. The mechanism, at least in part, is due to a decrease of nitric oxide mediated release of CGRP, rather than a decrease of CGRP gene expression.

[Effects of oxygen free radicals on myocardial alpha 1-adrenoceptor and its subtypes in rat].

The effects of oxygen free radicals on myocardial alpha 1-adrenoceptor and its subtypes and beta-adrenoceptor were observed by the method of radioligand binding assay in rat. The experiments showed: (1) .OH and O??? reduced the Bmax of alpha 1-adrenoceptors binding to 125IBE2254 by 55% and 36%, respectively. (2) The KI values of alpha 1-adrenoceptors were increased by .OH (by 171%), but not by O2-. (3) Both .OH and O2-. increased the ratio of alpha 1A vs alpha 1B subtypes. (4) beta-adrenoceptors were not changed by either .OH or O2-. (5) Oxygen free radical scavengers mannitol and superoxide dismutase were capable of preventing the changes of alpha 1-adrenoceptor and its subtypes induced by oxygen free radicals. The above results suggest that oxygen free radicals can reduce the number and affinity of myocardial alpha 1-adrenoceptors, of which the alpha 1B subtype is more accessible to the changes.