[Mechanism of catgut embedding at back-shu points for nonalcoholic steatohepatitis based on IKK/IKB/NF-κB signaling pathway].

OBJECTIVE: To explore the mechanism of catgut embedding at back-shu points on nonalcoholic steatohepatitis (NASH) in rats based on IKK/IKB/NF-κB signaling pathway and downstream inflammatory factors. METHODS: Eighty SPF SD rats were selected, among them 10 rats were selected divided into a normal group (group A), and the remaining 70 rats were fed with high-fat diet to establish NASH model. At the end of 12 weeks, 10 rats were randomly selected to verify whether the model establishment was successful. Then the remaining 60 rats were randomly divided into a model group (group B), a catgut embedding at back-shu points group (group C), a catgut embedding at abdominal points group (group D), an acupuncture at back-shu points group (group E), a sham catgut embedding group (group F) and a western medication group (group G), 10 rats in each group. The rats in the group C were treated with catgut embedding at "Ganshu" (BL 18), "Pishu" (BL 20), "Weishu" (BL 21) and "Shenshu" (BL 23); the rats in the group D were treated with catgut embedding at "Daheng" (SP 15), "Fujie" (SP 14), "Huaroumen" (ST 24) and "Tianshu" (ST 25); the rats in the group E were treated with acupuncture at the same acupoints as the group C; the rats in the group F were treated with catgut embedding at back-shu points but the needle did not enter subcutaneous tissue gamma; the rats in the group G were treated with intragastric administration of vitamin E capsule. All the treatment was given for 4 weeks. The rats in the group A were fed with normal diet until the end of 16 weeks without any intervention. The rats in the group B continued to be fed with high-fat diet until the end of 16 weeks. After the intervention, the liver index was calculated; the liver histomorphology was observed by HE staining; the liver function [alanine aminotransferase (ALT), gamma glutamyl transferase (γ-GGT), alkaline phosphatase (ALP)] and blood lipid [serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL)] were measured by serum biochemistry. The serum levels of TNF-α, IL-6 and IL-1ßwere detected by ELISA, and the expressions of IKK-α, NF-κBp65, IL-6, IL-1ß and TNF-α proteins in liver tissue were detected by Western blot. The temperature of the conception vessel and the governor vessel was measured by infrared thermography. RESULTS: Compared with the group A, the obvious steatosis and inflammatory cell infiltration were observed in the group B, and the body weight, liver wet-weight and liver index were all increased (P<0.01). Compared with the group B, the liver tissue morphology in the group C, the group D, the group E and the group G was improved in varying degrees, and the liver index was decreased (P<0.05), which was the most significant in the group C (P<0.05). Compared with the group A, the ALT, γ-GGT, ALP, TG, TC, LDL, TNF-α, IL-6 and IL-1ß were all increased in the group B (P<0.01); compared with the group B, the ALT, γ-GGT, ALP, TG, TC, LDL, TNF-α, IL-6 and IL-1ß in all intervention groups were all decreased in varying degrees (P<0.01, P<0.05), which was the most significant in the group C (P<0.01). Compare with the group A, the expressions of IKK-α, NF-κBp65, TNF-α, IL-6 and IL-1ßproteins in the group B were all increased (P<0.01); compared with the group B, the expressions of IKK-α, NF-κBp65, TNF-α, IL-6 and IL-1ßproteins in all intervention groups were decreased in varying degrees (P<0.05), which was the most significant in the group C (P<0.01). Compared with the group A, the temperature of the conception vessel and governor vessel was decreased in the group B (P<0.01). Compared with the group B, the temperature of the conception vessel and governor vessel was all increased in the group C, the group D and the group E (P<0.01); the temperature of the conception vessel in the group C was similar to that in the group D (P>0.05), while the temperature of the governor vessel in the group C was superior to that in the group D (P<0.05). CONCLUSION: The catgut embedding at back-shu points might inhibit the activation of IKK/IKB/NF-κB signaling pathway to interrupt the inflammatory cascade, and reduce the "second hit" of inflammatory factors on liver, which could slow down NASH progress and prevent and treat NASH.

Inhibition of S-Adenosylhomocysteine Hydrolase Induces Endothelial Dysfunction via Epigenetic Regulation of p66shc-Mediated Oxidative Stress Pathway.

BACKGROUND: Elevated levels of S-adenosylhomocysteine (SAH), the precursor of homocysteine, are positively associated with the risk of cardiovascular disease and with the development and progression of atherosclerosis. However, the role of SAH in endothelial dysfunction is unclear. METHODS: Apolipoprotein E-deficient ( apoE-/-) mice received dietary supplementation with the SAH hydrolase (SAHH) inhibitor adenosine dialdehyde or were intravenously injected with a retrovirus expressing SAHH shRNA. These 2 approaches, along with the heterozygous SAHH gene knockout ( SAHH+/-) mouse model, were used to elevate plasma SAH levels and to examine the role of SAH in aortic endothelial dysfunction. The relationship between plasma SAH levels and endothelial dysfunction was also investigated in human patients with coronary artery disease and healthy control subjects. RESULTS: Plasma SAH levels were increased in SAHH+/- mice and in apoE-/- mice after dietary administration of adenosine dialdehyde or intravenous injection with SAHH shRNA. SAHH+/- mice or apoE-/- mice with SAHH inhibition showed impaired endothelium-dependent vascular relaxation and decreased nitric oxide bioavailability after treatment with acetylcholine; this was completely abolished by the administration of the endothelial nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. Furthermore, SAHH inhibition induced production of reactive oxygen species and p66shc expression in the mouse aorta and human aortic endothelial cells. Antioxidants and p66shc siRNA prevented SAHH inhibition-induced generation of reactive oxygen species and attenuated the impaired endothelial vasomotor responses in high-SAH mice. Moreover, inhibition of SAHH induced hypomethylation in the p66shc gene promoter and inhibited expression of DNA methyltransferase 1. Overexpression of DNA methyltransferase 1, induced by transduction of an adenovirus, was sufficient to abrogate SAHH inhibition-induced upregulation of p66shc expression. Finally, plasma SAH levels were inversely associated with flow-mediated dilation and hypomethylation of the p66shc gene promoter and positively associated with oxidative stress levels in patients with coronary artery disease and healthy control subjects. CONCLUSIONS: Our findings indicate that inhibition of SAHH results in elevated plasma SAH levels and induces endothelial dysfunction via epigenetic upregulation of the p66shc-mediated oxidative stress pathway. Our study provides novel molecular insight into mechanisms of SAH-associated endothelial injury that may contribute to the development of atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03345927.

[Acupuncture and moxibustion based on meridian differentiation for cervical spondylosis radiculopathy:a randomized controlled trial].

OBJECTIVE: To observe the difference of clinical effects of acupoints selected based on meridian differen-tiation and conventional method for cervical spondylosis radiculopathy(CSR) treated with acupuncture and moxibustion. METHODS: Sixty patients with CSR were randomly divided into an observation group and a control group,30 cases in each one. Ashi points of the injured meridians in the neck,namely six-he points,were selected in the observation group,matched with luo-connecting points of the injured meridians on the same side and the interiorly-exteriorly correlated meridians on the opposite side. Conventional acupuncture was used on Fengchi(GB 20),Jiaji(EX-B 2) of the neck,Tianzhu(BL 10),Jianjing(GB 21),Houxi(SI 3),Hegu(LI 4) and Waiguan(TE 5) on the affected side in the control group. Treatment was given once every other day,three times a week and total 12 times in the two groups. Twenty subscales for CSR and visual analogue scale(VAS) were observed before and after treatment,and total effects were evaluated after treatment. RESULTS: The effective rate of the observation group was 93.3%(28/30),which was better than 66.7%(20/30) of the control group(P<0.05). The scores of 20 subscales and VAS after treatment were all improved compared with those before treatment in the two groups(all P<0.01),with more apparent change in the observation group(both P<0.05). CONCLUSIONS: The effect of acupuncture and moxibustion based on meridian differentiation is obvious,and superior to that of conventional acupoints selection.