Objective To explore the feasibility of establishing a modified mouse model of pressure overload induced left ventricular hypertrophy by transverse aortic constriction(TAC).Methods 55 C57BL/6 female mice were randomly divided into three groups:severe TAC group (n =27),moderate TAC group (n =7) and sham surgery group (n =21),respectively.By ligating the aorta arch between innominate artery and the left common carotid artery with modified techniques in a minimally invasive way,moderate or severe aortic constriction were established successfully and reliably to mimic left ventricular(LV)outflow obstruction; to correctly evaluate the cardiac structural and functional responses to aortic arch banding,2-dimention (2D) and M mode transthoracic echocardiography (TTE) were deployed to monitor the LV contractile function and assess the LV hypertrophic changes induced by pressure overload at 4 weeks after the surgery.Results The mouse model of aortic constriction was established successfully with a post-operative survival rate more than 88％.And all these operated mice were able to survive at least 4 weeks long.Eccentric left ventricular hypertrophic changes were detected with echocardiographic measurement 4 weeks after the banding operation in both mTAC and sTAC group,as dilated left ventricular lumen with enlarged LV end-diastolic dimension (LVEDD) and LV end systolic-dimension (LVESD) were confirmed.Mice with moderate banded aorta exhibited a compensated LV hypertrophy with preserved contractile functions and satisfactory ventricular wall movements to some extent,although left ventricular fractional shorting (LVFS) reduced gradually from 0.403 ± 0.007 to 0.340 ± 0.015 (P＜0.05) ; while in severe banded (sTAC) mice,LVFS reduced more significantly as a sharp decrease from 0.438 ± 0.011 to 0.216 ± 0.012 (P ＜ 0.01) were detected,combined with poor contractile function and stiff ventricular wall movements,exhibiting a de-compensated pathological left ventricular hypertrophy.Conclusion This modified TAC opcration could be easily carried out,and the TAC mouse model mentioned in the present research was an effective pressure overload model with several superiorities including less trauma,improved post-operative survival rate,rapid recovery and satisfactory reproducibility,thus a better and recommended mouse model for specific research purpose concerning LV hypertrophy mechanistic studies.

Objective To predict and verify the upstream regulatory microRNA (miRNA)of protein kinase D1 (PKD1),and to investigate its role in cerulein induced acute pancreatitis (AP)in rats. Methods Potential up-stream regulatory miRNA of PKD1 was predicted by using bioinformatics software. Dual luciferase reporter gene system and Western blot were applied to verify the regulation of PKD1 by the selected miRNA. Experimental AP was induced by 6 intraperitoneal injection of cerulein (20 μg/ kg)at hourly intervals after administration of the CY5 - labeled notar-get control (AP group,n = 20)or selected miRNA (treatment group,n = 20),respectively by intraperitoneal injection into rats. Other rats were divided randomly into a normal control group (n = 10)without any treatment. Besides 10 rats in either AP or treatment group were sacrificed 6 hours after the first injection of cerulein,and the rats were all sacri-ficed 24 hours after the first injection. The blood samples and pancreatic tissues of each rat were collected to test serum amylase and lipase activities,or to make hematoxylin - eosin stain for AP pathological scores as well as PKD1 immuno-histochemical staining,respectively. Results TargetScan 7. 1 software analysis showed that miR - 128 - 3p was the po-tential upstream regulatory miRNA of PKD1,which was verified by dual luciferase reporter gene system and Western blot detection. Compared to the normal control group,serum amylase and lipase activities after 6 h exposure to cerulein increased in both AP group and the treatment group[13313. 00(9424. 00 - 15995. 00)U/ L,13552. 00(10399. 50 -18408. 25)U/ L vs. 1430. 50(1214. 25 - 1543. 25)U/ L;547. 00 (515. 00 - 627. 00)U/ L,857. 50(522. 00 -1222. 25)U/ L vs. 34. 00(32. 50 - 34. 75)U/ L],and the differences were significant(χ2 = 8. 715,P < 0. 05;χ2 =9. 115,P < 0. 05),which indicated that the rat models of AP were successfully established. The immunohistochemical scores of PKD1 after 24 h exposure to cerulein decreased in the treatment group[0. 50(0 - 2. 75)scores],compared with the normal control group [4. 00(4. 00 - 8. 00)scores]and the AP group [4. 00(3. 75 - 8. 00)scores],and difference was significant(χ2 = 18. 302,P < 0. 05). Accordingly,the total pathological scores of HE staining decreased significantly in the treatment group,as compared to the AP group (3. 80 ± 0. 85 vs. 6. 90 ± 1. 15,t = 4. 481,P < 0. 01). The results showed that the inflammatory cell infiltration and tissue necrosis were significantly improved after miR -128 - 3p treatment. Conclusions miR - 128 - 3p is the upstream regulatory microRNA of PKD1 which protects pan-creata from necrotic injury and inflammatory cell infiltration in PKD1 - mediated acute pancreatitis.