Role of eNOS/PKG-1 pathway in L-Arginine against right ventricular remodeling induced by monocrotaline in rats / 中国药理学通报

Aim To investigate the role of eNOS/PKG- 1 pathway in L-arginine (L-arg) intervention in right ventricular remodeling induced by monocrotaline (MCT) in Sprague Dawley (SD) rats with the aid of the tool medicine L-NAME. Methods Twenty SD rats were randomly divided into control group, MCT group, L-Arg group and L-Arg + L-NAME group. The general condition of rats was observed; the right ventricular pressure of rats was measured by right heart catheterization; the rats and the right ventricle were weighed and the right ventricular mass index was calculated; the morphological changes of the right ventricular were observed by H&E staining; the protein expressions of cTnl, eNOS and PKG-1 were detected by Western blot in the right ventricular. Results Compared with control group, right ventricular max pressure and right ventricular mass index significantly increased ( P < 05) ; the weight of rats in MCT group was significantly reduced ( P < 0. 05); the right ventricular myocytes were hypertrophic, disordered and infiltrated with inflammatory cells; the protein expression of cTnl was obviously up-regulated ( P < 0. 05 ) ; the protein expressions of eNOS and PKG-1 were significantly down- regulated ( P < 0. 05 ) . L-arg could significantly improve the above changes ( P < 0. 05 ). However, the effects of L-arg were inhibited by eNOS inhibitor L- NAME. Conclusions L-arg can improve the right ventricular remodeling in rats induced by MCT, and the mechanism may be related to the up-regulation of the protein levels of eNOS and PKG-1.

Icariin improves myocardial fibrosis induced by isoproterenol via regulating expression of a-SMA and MMPs/TIMP / 中国药理学通报

Abstract; Aim To explore the effect of icariin (ISO) in mice. Methods C57BL/6 mice were ran- (ICA) on myocardial fibrosis induced by isoproterenol domly divided into control group, ISO group, low-dose (15 mg • kg"1), middle-dose (30 mg • kg"1) and high-dose (60 mg • kg"1) of ICA-treated group and Losartan-treated group ( 9 mg • kg"1 ). The control group was subcutaneously injected with normal saline, and the other groups were subcutaneously injected with ISO (5 mg • kg"1, qd) continuously 14 days to established the myocardial fibrosis model. The ICA-treated groups and Losartan-treated group were simultaneously intragastrically administered of ICA or Losartan, respectively. And the other groups received the same a- mount of double distilled water. The left ventricular e- jection fraction (LVEF) and the left ventricular fraction shortening rate ( LVFS) were evaluated by the small animal ultrasound. The heart mass index (HMI) was calculated. The left ventricular collagen deposition was detected by Masson staining. The protein expressions of a-SMA, MMP-2, MMP-9 and TIMP-1 in the left ventricular tissue were detected by Western blot. Results ICA (30, 60 mg • kg"1) and Losartan could inhibit the decreased LVEF and LVFS, the increased HMI and left ventricular collagen deposition, the up- regulated a-SMA and MMP-9 protein expression, the down-regulated MMP-2 and TIMP-1 protein expression in the left ventricular tissues induced by ISO. Conclusions ICA can improve myocardial fibrosis induced by ISO in mice, and the underlying mechanism may be related to the regulation of the protein expression of a- SMA and MMPs/TIMP-1.

Icariside Ⅱ ameliorates myocardial fibrosis in spontaneously hypertensive rats through regulating expression of MMP-2, MMP-9 and TIMP-1 / 中国药理学通报

Aim To investigate the effects of IcarisideⅡ ( ICS Ⅱ) on myocardial fibrosis in spontaneously hypertensive rat( SHR) . Methods Twenty male SHR rats were randomly divided into the model group (group SHR) , ICS Ⅱ low ( ICS Ⅱ-L) , middle ( ICSⅡ-M) and high ( ICS Ⅱ-H) group, and male WKY rats were set as control group ( group WKY) . ICS Ⅱ-L, ICSⅡ-M and ICSⅡ-H groups were intragastrically administered with ICS Ⅱ for 12 weeks. After that the blood pressure was measured in rats. Then, the rats were sacrificed and the left ventricles were separated in order to calculate the left ventricular mass index. Mas-son staining was used to detect the occurrence of inter-stitial fibrosis in cardiac tissues. Real time PCR was used to observe the gene expression of MMP-2, MMP-9 and TIMP-1 in the left ventricle in SHRs. The protein expression levels of MMP-2, MMP-9, TIMP-1, Colla- gen Ⅰ and Collagen Ⅲ were measured by Western blot. Results Compared with SHR group, the myo-cardial fibrosis was reduced after ICS Ⅱ (8, 16 mg· kg-1) treatment. The blood pressure and left ventricu-lar mass index decreased(P<0.05). The expressions of MMP-2, MMP-9, CollagenⅠand CollagenⅢwere down-regulated in left ventricular tissues( P <0.05 ) , while the expression of TIMP-1 was up-regulated( P<0.05) . Conclusion Icariside Ⅱ ameliorates myocar-dial fibrosis in SHR, and the mechanisms might be re-lated to the decrease of blood pressure and down-regu-lation of MMP-2, MMP-9 expression and up-regulation of TIMP-1 expression.

Incidence and risk factors of early deep venous thrombosis after knee arthroscopy operation under conventional tourniquet / 中国骨伤

<p><b>OBJECTIVE</b>To find out the incidence of early DVT in patients after knee arthroscopic surgery with routine use of tourniquet and discuss the associate risk factors.</p><p><b>METHODS</b>Total 1 561 cases undertaken primary knee arthroscopic surgery was reviewed retrospectively from January 2013 to January 2017, including 651 males and 910 females with a mean age of (65.7±8.7) years old ranging from 62 to 81 years old. The cases were divided into DVT group and non-DVT group according to ultrasonic Doppler after surgery. The DVT occurrence rate was calculated and the basic information was analyzed to filter out the risk factors through univariate analysis and multivariate analysis. The cases of DVT group received 6 months anticoagulation therapy and were undertaken a follow-up of 1, 3, 6 months by ultrasonic Doppler.</p><p><b>RESULTS</b>Out of the 1 561 cases, 226(14.5%) developed early DVTs following surgery, 32(2.0%) cases had the proximal DVTs, and 194(12.4%) cases had the isolated distal DVTs. The risk factors include the age(>=73 years), female sex and gastrocnemius vein dilation (GVD), hypertension, longer tourniquet time(>=74 min). The GVD and the length of tourniquet time was considered to be the best predictor of the early DVTs after surgery, with an odds ratio of 2.337 (95% CI, 1.644-3.611) and 2.112 (95%CI, 1.452-3.301). Twelve isolated distal DVTs(6.6%) and 11 proximal DVTs(36.7%) still showed thrombus at 6-month follow-up, but exhibit decreased size and at various stage of resolution.</p><p><b>CONCLUSIONS</b>The incidence of early DVTs after knee arthroscopic surgery is 14.5%. Out of all risk factors, the GVD and the length of tourniquet time have the best power for prediction of DVTs after surgery. Both proximal and distal DVTs received accepted outcomes after formal therapy.</p>

Study on Improvement Effect and Mechanism of Icariin on Renal Lesion in Rats with Spontaneous Hyper-tension / 中国药房

OBJECTIVE:To observe the effect of pathological lesion of renal tissue in rats with spontaneous hypertension (SHR),and study its mechanisms based on nuclear factorκB(NF-κB)signaling pathway. METHODS:21 SHR were randomly di-vided into model group and ICA low-dose,high-dose groups(20,40 mg/kg,denoted by ICA-L,ICA-H groups);other 7 homolo-gous Kyoto rats (WKY) were regarded as control group. All rats were intragastrically administrated,twice a day,for 11 weeks, rats in control group and model group received equal volume of double distilled water,ig. Pathological changes in renal tissue in each group were observed;Western blot method was used to detect protein expressions of p-NF-κB-p65,IκB and TNF-α in renal tissue. RESULTS:Compared with control group,model group showed disorder renal structure,narrow and irregular glomerular cysts;the protein expression of IκB was significantly down-regulated,protein expressions of p-NF-κB-p65 and TNF-α were signifi-cantly up-regulated(P0.05). CONCLUSIONS:ICA plays a role in improving renal pathological lesion in SHR,and the mechanism may be related to inhibiting NF-κB signaling pathway.

Anti-apoptotic effect of Icariin on renal tubular epithelial cell in SHR / 中国药理学通报

Aims To observe the effect of Icariin( Ica) on apoptosis of renal tubular epithelial cell in spontane-ously hypertensive rats( SHR) , and to explore its pos-sible mechanism. Methods 21 male SHR of 14 weeks were randomly divided into model groups, the Ica low and high dose groups (20 or 40 mg·kg-1 ,ig, bid, to 26 weeks ) , 14 week-old male homologous Kyoto rats ( WKY ) as control group, and the number of each group was 7 . WKY group and model group were ad-ministered by gavage with the same volume of double distilled water. The pathological changes were observed by using the HE staining and the apoptosis was detec-ted by TUNEL method in renal tubular epithelial cell, respectively. The mRNA levels of Bok, Bax, Bcl-2 were detected by the real time RT-PCR and the protein expressions of Bcl-2 , Bax and Active caspase-3 were detected by Western blot method in the renal tissue. Results Compared with WKY, renal capsule was nar-row and irregular, and glomerular mesangial matrix was increased with the cell arrangement disorder and the capillary dilation and congestion. Several glomeruli shrank and renal tubular epithelial cell was edema with luminal stenosis in model group. The apoptosis of renal tubular epithelial cell was evident and the mRNA levels of Bok and Bax, as well as the protein expressions of Bax and Active caspase-3 were significantly up-regula-ted in model group, while the mRNA Level and protein expression of Bcl-2 significantly down-regulated ( P <0. 05 or P<0. 01). Compared with model group, renal glomerular capsule widened, proliferation of glomerular mesangial matrix was reduced, and cell arrangement disorder and capillary dilation and renal tubular lumen stenosis were improved in Ica group. Renal tubular ep-ithelial cell apoptosis was decreased evidently, and the mRNA level of Bax, Bok and protein expression of Bax were significantly down-regulated in Ica group, and the mRNA level and protein expression of Bcl-2 in Ica-H group were significantly up-regulated while the protein expression of Active caspase-3 significantly down-regu-lated( P <0. 05 or P <0. 01 ) . Conclusion Ica can inhibit the apoptosis of renal tubular epithelial cell in spontaneously hypertensive rats and its mechanism may be related to the down-regulation of Bok, Bax, and Active caspase-3 , accompanied with the up-regulation of Bcl-2 .

Icariin attenuates left ventricular remodeling in SHR by up-regulating PPARαand PPARγ / 中国药理学通报

Aim To investigate the effect of Icariin ( Ica) on remodeling of left ventricular in SHR and ex-plore the mechanism. Methods Twenty-one male SHR aged 14 weekswere randomly divided into model group(n=7), low-dose of Ica-treated group(20 mg· kg-1 . bid, n =7 ) , high-dose of Ica-treated group ( 40 mg·kg-1. bid,n=7), and WKY as control group(n=7 ) . Low- and high-dose of Ica-treated groups were given Ica from the age of 14 weeks to 26 weeks. The other rats in the model group and control group were given the same amount of double distilled water. Then, the content of hydroxyproline ( Hyp) was measured by ELISA. The morphological changes of the left ventricu-lar were observed by Masson staining. The mRNA and the protein expression of PPARα and PPARγ were ex-amined by real time RT-PCR and Western blot tech-nique respectively. Results Compared with the nor-mal control group, interstitium fibrosis and myofibrilla were lined up in disorder; the content of Hyp was in-creased and the mRNA and protein expression of PPARα and PPARγ were down-regulated in model group(P<0. 01). Compared with the model group,the myocardial cells were arranged less disorderly and the myocardial fibrosis was reduced; the content of Hyp was decreased in low-and high-dose of Ica-treated groups(P<0. 01 or P<0. 05);the mRNA and protein expression of PPARα and PPARγwere up-regulated in low- and high-dose of Ica-treated groups ( P <0. 01 or P<0. 05 ) . Conclusion Ica may attenuate left ven-tricular remodeling in SHR by up-regulating PPARαand PPARγ.

Osthole could attenuate right ventricle remodeling in monocrotaline-treated rats by up-regulating PPARαand PPARγ / 中国药理学通报

Aim To explore the effect of Osthole (Ost)on the right ventricle remodeling in monocrot-alinetreated rats and the possible mechanism.Meth-ods ♂ SD rats were randomly divided into normal control group,model group,low dose of Ost treatment group (10 mg·kg -1 )and high dose of Ost treatment group (20 mg·kg -1 ).All rats were given a single dose of MCT 50 mg·kg -1 subcutaneously to establish the right ventricle remodeling except normal control group.Then the rats in Ost treatment group were ga-vaged once daily.After 28 days of administration,the right ventricle(RV)and left ventricle plus septum(LV+SEP)were weighed separately.RV hypertrophy in-dex (RVHI)were measured by the relative weight rati-o of RV to LV +SEP.The morphological changes of right ventricle were executed by HE staining.The pro-tein expression of PPARαand PPARγwere detected by Western blot.Results Compared with the control group,RVHI was increased obviously (P <0.05 ), myocardial hypertrophy and structure disorders were observed in model group.The protein expression of PPARαand PPARγwere down-regulated significantly in model group (P <0.05).Compared with the model group,the value of RVHI (P <0.05),myocardial hy-pertrophy,structure disorders were improved signifi-cantly in Ost treatment group.The protein expression of PPARαand PPARγwere up-regulated in Ost treat-ment group (P <0.05).Conclusion Ost can attenu-ate the right ventricle remodeling induced by MCT in rats,which may be related to up-regulating the expres-sion of PPARαand PPARγ.

Icariin attenuates renal interstitial fibrosis by reducing aldosterone in SHR / 中国药理学通报

Aim To investigate the effect of icariin ( ICA) on renal interstitial fibrosis in SHR and explore its mechanism. Methods Fourteen male SHR of 13-week-old were randomly divided into model group( n=7 ) and ICA group ( n=7 ) , and WKY as control group (n=7). One week after adaptive breeding,the rats in the ICA group were given ICA 40 mg·kg-1,ig,bid to 26-week-old. The other rats in the model group and control group were given the same amount of normal sa-line. Then, the morphological changes of the kidney were observed by HE and Masson staining,respective-ly. The contents of plasma aldosterone andⅢcollagen were measured by double antibody sandwich method. The mRNA expressions of TGF-β1 , Smad2 , CTGF and FN were examined by real time RT-PCR. Results Compared with the normal control group, the kidney structures of model group were disordered,the mesang-ial matrix and the tubular interstitial fibrosis were in-creased. The contents of plasma aldosterone and Ⅲcollagen were increased in model group ( P <0. 01 ) . And the mRNA expressions of TGF-β1 , Smad2 , CTGF and FN in kidney tissues were up-regulated in model group( P <0. 01 or P <0. 05 ) . Compared with the model group,the kidney structures were improved and the contents of plasma aldosterone and Ⅲ collagen were reduced, as well as the mRNA expressions of TGF-β1,Smad2,CTGF and FN in kidney tissues were down-regulated(P<0. 01 or P<0. 05)in ICA group. Conclusion ICA may have anti-renal interstitial fi-brosis effect on SHR,and the mechanism might be re-lated to the reduced plasma aldosterone levels and the down-regulated expression of TGF-β1 and Smad2 .

Impacts of bicyclo-monoterpene enhancers on transdermal delivery of ligustrazine / 药学学报

The purpose of this study is to investigate the impacts of bicyclo-monoterpene promoters (i.e., borneol and camphor) on the in vitro permeation of ligustrazine (LGT) through the hairless porcine dorsal skin. Fourier transform-infrared (FT-IR), scanning electron microscope (SEM) and transdermal delivery kinetics in vitro were performed to investigate the effect of the promoters on the biophysical changes to the stratum corneum (SC), the surface changes to porcine skin and the in vitro percutaneous fluxes of ligustrazine through procine skin. FT-IR results revealed that the peak shift and the decrease in the peak area with borneol were higher than those with camphor. SEM studies demonstrated that the morphological change to SC was related to the chosen enhancer. It was observed that the SC lipid extraction with borneol and camphor led to disruption of the SC and the scutella desquamation. Apparent density (AD) was utilized to describe the desquamation extent of the scutella. Percutaneous fluxes of ligustrazine through porcine skin were evaluated in vitro by the Franz-type diffusion cells. Use of borneol led to greater penetration of ligustrazine across porcine skin. It was shown that the permeation enhancement mechanism of bicyclo-monoterpenes to ligustrazine included extracting and disordering lipids which involved the shift changes in C-H stretching and H-bonding action between enhancers and cermaide. The penetration capability of the hydroxy groups in bicyclo-monoterpenes was better than that of the ketone groups.

Develop a statistics analysis software in population genetics using VBA language / 法医学杂志

OBJECTIVE@#To develop a statistics analysis software that can be used in STR population genetics for the purpose of promoting and fastening the basic research of STR population genetics.@*METHODS@#Selecting the Microsoft VBA for Excel, which is simple and easy to use, as the program language and using its macro function to develop a statistics analysis software used in STR population genetics.@*RESULTS@#The software "Easy STR Genetics" based on VBA language, by which the population genetic analysis of STR data can be made, were developed.@*CONCLUSION@#The developed software "Easy STR Genetics" based on VBA language, can be spread in the domain of STR population genetics research domestically and internationally, due to its feature of full function, good compatibility for different formats of input data, distinct and easy to understand outputs for statistics and calculation results.