ABSTRACT
Objective To observe the dynamic changes of cardiac lymphangiogenesis in Doxorubicin(DOX)-induced dilated cardiomyopathy(DCM)model mice,and to study the the protective mechanism of Kuoxin Decoction.Methods The DCM mouse model was established by intraperitoneal injection of DOX,and the dynamic observation was performed every week.On this basis,60 C57BL/6 mice were randomly divided into 6 groups(n=10):control group,Model group,L-KXD,M-KXD and H-KXD groups and Captopril group.After successful modeling,the KXD and the positive control drug Captopril were administered continuously for 28 days.Echocardiography was used to detect cardiac function in mice,HE staining and Masson staining were used to observe pathological and morphological changes of the heart,Whole-mount immunofluorescent staining was used to detect the expression of LYVE-1 and Podoplanin in epicardial lymphatic vessels,Western blot was used to detect the expression of VEGFR-3 protein,and qPCR was used to detect the expression of VEGFR-3 mRNA.Results DCM mice induced by DOX showed significant cardiac function decline from the third week(DOX:15 mg·kg-1,P<0.05),and significant ventricular remodeling at the fifth week(DOX:15 mg·kg-1,P<0.01);The lymphatic vessel area of the mouse heart decreased significantly from the fourth week(DOX:20 mg·kg-1,P<0.0001),and the expression of VEGFR-3 decreased significantly from the third week(DOX:15 mg·kg-1,P<0.01).Conclusion KXD can improve ventricular remodeling and cardiac function in DOX-induced DCM mice,promote cardiac lymphangiogenesis,and upregulate the expression of VEGFR-3 at protein and mRNA levels,with a better effect than captopril.DOX-induced cardiac lymphangiogenesis in DCM mice leads to severe myocardial fibrosis and weakened cardiac function,which gradually worsens with the accumulation of modeling time and dose.KXD can promote cardiac lymphangiogenesis and improve cardiac function in DOX-induced DCM mice.The mechanism may be related to the up-regulation of VEGFR-3 expression.
ABSTRACT
Objective: To explore the lipid-lowering effect and potential mechanism of the couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris on hyperlipidemia rats. Methods: Forty-eight Sprague-Dawley rats were randomly divided into 6 groups, normal control group, high-fat model group, simvastatin group, Tribulus terrestris group, Flastem Milkvetch Seed group, and couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris group, with 8 rats in each group. The normal control group was fed with basal diet, and the other groups were fed with high-fat diet to establish a hyperlipidemia rat model. At the same time, different group rats were treated with different drug respectively. 6 weeks later, the body weight and visceral index of the rats were measured. Levels of serum cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected by automatic biochemical analyzer. The mRNA and protein expression of HMG coenzyme A reductase (HMGCR), cholesterol 7-alpha hydroxy-lase (CYP7A1) and low density lipoprotein receptor (LDL-R) were detected by RT-PCR and western blot. Results: Compared with model group, the serum levels of TC, TG, and LDL-C were significantly decreased in all Chinese medicine groups, and the serum level of HDL-C was significantly increased in Flastem Milkvetch Seed group and couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris group. Moreover, the mRNA and protein expression of HMGCR, CYP7A1, and LDL-R in rat liver also significantly increased in all Chinese medicine treatment groups. And couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris group shows more significantly effect. Conclusion: Couplet medicines of Flastem Milkvetch Seed and Tribulus terrestris significantly regulate the serum lipid levels on hyperlipidemia rat model, and its mechanism may be related to the regulating expressions of HMGCR, CYP7A1, LDL-R gene.
ABSTRACT
Objective Lipid metabolism disorder can lead to male sterility, but its mechanism of affecting spermatogenesis and testis microenvironment remains unclear.This study aimed to investigate the effects of high fat diet on reproductive function and the expression of Ox-LDL within testis in male mice. Methods 16 C57BL/6 mice aged 8 weeks were divided into two groups by random number table method.High fat diet group was fed with high fat diet while normal fat diet group was fed with normal fat diet .At the end of 16 weeks, the levels of TG, TC, Ox-LDL and testosterone in serum were measured.The sperm concentration and motility from caudal epi-didymis were analyzed.The testis structure was observed by HE stai-ning.The localization and expression of Ox-LDL in testis were detec-ted by immunohistochemical technique. Results Compared with the normal diet group mice, the body weight (P0.05).The serum level of testosterone[(3.64 ±0.43)mg/L vs (0.40 ±0.14) mg/L, P<0.01], the sperm concentration[(9.95 ±0.75)106/mL vs (5.66 ±1.51)106/mL, P<0.01] and the sperm motility[(54.69 ±17.84)%vs (32.48 ±5.80)%, P<0.01] decreased in high fat diet group significantly.HE staining also showed that the amount of Leydig cells, spermatids and spermatozoons reduced obvi-ously in high fat diet group.Immunohistochemistry staining showed that Ox-LDL was mainly distributed around Leydig cells of mice tes-tis.The expression of Ox-LDL in high fat diet group increased significantly ( P<0.01) . Conclusion The expression of Ox-LDL in Leydig cells of high fat diet C57BL/6J mice increases significantly, which may inhibit testosterone biosynthesis and affect spermatogen-ic function.