Electroacupuncture improving obesity-induced insulin resistance via regulating intestinal SIRT1/TLR4 signaling pathway. / ç”µé’ˆè°ƒæŽ§å°è‚ æ²‰é»˜ä¿¡æ¯è°ƒèŠ‚å› å­1/Tollæ ·å—ä½“4ç‚Žæ€§é€šè·¯æ”¹å–„è‚¥èƒ–å¤§é¼ èƒ°å²›ç´ æŠµæŠ—çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) in obese rats with insulin resistance (IR) through regulating intestinal silent information regulator 1 (SIRT1)/Toll-like receptor 4 (TLR4) signaling pathway, so as to explore the underlying mechanism of EA in improving obesity-induced IR. METHODS: A total of 40 Wistar rats were randomly divided into 4 groups, i.e. normal group, model group, EA group and EA combined with inhibitor group, with 10 rats in each group. The obesity-induced IR model was induced by feeding high-fat diet for 8 weeks. EA (2 Hz, 1mA) was applied at "Zhongwan"(CV12), "Guanyuan"(CV4), "Zusanli"(ST36) and "Fenglong" (ST40) for 10 min, 3 times a week for 8 weeks in both EA and EA combined with inhibitor groups. Sirtinol, an inhibitor of SIRT1 was injected into the tail vein (1 mg/kg), 3 times a week for 8 weeks in EA combined with inhibitor group. The body weight, glucose infusion rate (GIR) of rats in each group were recorded. The contents of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and lipopolysaccharide (LPS) were detected by ELISA. Mucosal morphological changes in the small intestine was observed by HE staining and was graded using Chiu's score. The protein relative expression levels of SIRT1 and TLR4 and the co-labeling of SIRT1 with TLR4 in the small intestine was detected by Western blot and double immunofluorescence staining, separately. RESULTS: Compared with the normal group, the body weight, serum contents of CRP, TNF-α, IL-6, LPS, Chiu's score, TLR4 protein relative expression level and percentage of TLR4 positive expression area were increased (P<0.01, P<0.05), while the GIR, SIRT1 protein expression, percentage of SIRT1 positive expression area and SIRT1/TLR4 were decreased (P<0.01) in the model group. The pathological injury of small intestine mucosa was severe, accompanied with inflammatory cell infiltration in the model group. Following interventions, the body weight, serum contents of CRP, TNF-α and LPS, Chiu's score, TLR4 protein relative expression level and percentage of TLR4 positive expression area were decreased(P<0.01, P<0.05), and the GIR was increased (P<0.01), the pathological injury and inflammatory cell infiltration of small intestine mucosa were reduced in both EA and EA combined with inhibitor groups in contrast to the model group. Compared with the model group, the serum IL-6 content was significantly decreased (P<0.01), and the SIRT1 protein relative expression level and percentage of positive expression area, SIRT1/TLR4 were increased (P<0.01, P<0.05) in the EA group. Compared with the EA group, EA combined with inhibitor group showed the body weight, serum CRP, IL-6, LPS, Chiu's score, TLR4 protein relative expression level and TLR4 positive expression area were increased (P<0.01, P<0.05), and the GIR level , SIRT1 relative expression level, SIRT1/TLR4 ratio were decreased (P<0.05, P<0.01). CONCLUSIONS: EA can reduce the body weight and ameliorate peripheral insulin sensitivity in IR obese rats, which may be related with its function in regulating intestinal SIRT1/TLR4 signaling pathway to reduce inflammatory response.

[Immediate effect of acupuncture and moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) on heart rate variability in patients with qi deficiency syndrome].

OBJECTIVE: To compare the immediate effect of acupuncture and moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) on heart rate variability index in patients with qi deficiency syndrome. METHODS: Ninety patients with qi deficiency syndrome were randomly divided into an acupuncture group, a moxibustion group and a blank group, 30 patients in each group. The patients in the acupuncture group were treated with acupuncture at Guanyuan (CV 4) and Zusanli (ST 36) for 15 min; acupuncture was given once. The patients in the moxibustion group were treated with moxibustion with identical acupoints and treatment duration. The patients in the blank group received no intervention. The symptom scores of qi deficiency syndrome in each group before and after treatment were recorded. The average heart rate and index of heart rate variability including total power, low frequency (LF), high frequency (HF) and logarithm of LF/HF (log LF/HF) were tested 5 min before treatment, 5 min, 10 min, 15 min into treatment, and 5 min after treatment. RESULTS: The symptom scores of qi deficiency syndrome were reduced in the acupuncture group and moxibustion group after treatment (P<0.05). Compared before treatment, in the acupuncture group, the HF was increased 5 min into treatment (P<0.05), but was reduced 15 min into treatment and 5 min after treatment (P<0.05, P<0.01). The log LF/HF was increased 5 min and 10 min into treatment and 5 min after treatment (P<0.01). The difference of average heart rate between 5 min before treatment and 5 min after treatment in the acupuncture group was higher than that in the moxibustion group and blank group (P<0.05), and the difference of log LF/HF was higher than that in the moxibustion group and blank group (P<0.05, P<0.01). CONCLUSION: Acupuncture and moxibustion has immediate effects on heart rate variability in patients with qi deficiency syndrome, and the effect of acupuncture is superior to moxibustion, which may be related to the benign regulation of acupuncture on autonomic nervous system.

[Effect of electroacupuncture on silent information regulator 1, fork head transcription factor O1 and proopiomelanocortin in the hypothalamus of rats with obesity induced by high-fat diet].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on silent information regulator 1 (SIRT1), forkhead transcription factor O1 (FoxO1), and proopiomelanocortin (POMC) in the hypothalamus of rats with high-fat diet-induced obesity (DIO), as well as the mechanism of EA in regulating central appetite peptides to help lose weight. METHODS: Male Wistar rats were randomly divided into normal group, model group, EA group, EA＋inhibitor group, inhibitor group, and sham-operation group, with 10 rats in each group. High-fat diet was used to establish a rat model of DIO. The rats in the EA group and EA＋inhibitor group were given EA at "Fenglong" (ST40), "Zhongwan "(CV12)，"Guanyuan "(CV4), and"Zusanli" (ST36) with continuous wave at a frequency of 2 Hz and an intensity of 1 mA, for 10 minutes each time. The rats in the EA＋inhibitor group and inhibitor group were given tube placement in the third ventricle and injection of the specific SIRT1 antagonist EX-527. The rats in the sham-operation group were given tube placement in the third ventricle and injection of artificial cerebrospinal fluid. The above treatment was given 3 times a week for 8 weeks in total. Body weight, food intake, and Lee's index were observed before and after treatment. An automatic biochemical analyzer was used to measure the serum levels of total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA), and Western blot was used to measure the protein expression of SIRT1, FoxO1, acetylated FoxO1(AC-FoxO1), and POMC in the hypothalamus. RESULTS: Before treatment, the model group, the EA group, the EA＋inhibitor group, the inhibitor group, and the sham-operation group had significantly higher body weight and food intake than the normal group (P<0.01), and the model group and the sham-operation group had a significantly higher Lee's index than the normal group (P<0.05). Compared with the model group after treatment, the EA group and the EA＋inhibitor group had significant reductions in body weight, food intake, TC, and the protein expression of AC-FoxO1 (P<0.01, P<0.05) and significant increases in the protein expression of SIRT1, FoxO1 and POMC (P<0.01, P<0.05); the EA group had significant reductions in Lee's index and the levels of TG, FFA(P<0.05，P<0.01)；the inhibitor group had significant increases in food intake, the serum levels of TC, TG, FFA(P<0.01) and significant reductions in the protein expression of SIRT1, FoxO1 and POMC (P<0.01，P<0.05). Compared with the EA group, the EA＋inhibitor group and the inhibitor group had significant increases in body weight, food intake, Lee's index, the levels of TG, FFA and the protein expression of AC-FoxO1 (P<0.01, P<0.05) and significant reductions in the protein expression of SIRT1, FoxO1 and POMC (P<0.01); the inhibitor group had significant increases in the serum levels of TC (P<0.01). Compared with the EA＋inhibitor group, the inhibitor group had significant increases in body weight, food intake, the serum levels of TC, TG, FFA, and the protein expression of AC-FoxO1 (P<0.01), as well as significant reductions in the protein expression of SIRT1, FoxO1 and POMC (P<0.01). CONCLUSION: In rats with DIO, EA can effectively up-regulate the expression of SIRT1 in the hypothalamus, exert a deacetylation effect on FoxO1, and promote the expression of the downstream appetite-inhibiting peptide POMC, which may be one of the mechanisms of EA to help lose weight by regulating central appetite peptides in the obesity model.

[Electroacupuncture improves inflammatory reaction and insulin sensitivity in insulin-resistant obese rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on inflammatory reaction and insulin sensitivity in insulin-resistant obese (OIR) rats. METHODS: Thirteen male Wistar rats were randomly selected as the control group and fed with common diet. The other 39 rats were fed with high-fat diet for 8 weeks to establish OIR model and then randomized into model, EA and sham EA groups. EA (2 Hz, 1 mA) was applied to unilateral "Zusanli" (ST36), "Fenglong" (ST40), "Zhongwan" (CV12) and "Guanyuan" (CV4) for 15 min, once every other day for 8 weeks, and sham EA was applied to unilateral 4 control spots about 5 mm lateral to the aforementioned 4 acupoints after shallowly inserting acupuncture needles, but without electric current output. After 8 weeks' intervention, the body weight was recorded and the glucose infusion rate (GIR) measured using hyperinsulinemic-euglycemic clamp technique. At the 6th week of intervention, glucose contents of intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tole-rance test (IPITT) were measured. The levels of serum insulin (INS) and inflammatory factors as C-reactive protein (CRP), IL-6 and TNF-α were measured by using ELISA at the end of the treatment. The expression levels of IL-6, TNF-α, monocyte chemoattractant protein-1(MCP-1), IL-10 and IL-1ß proteins and mRNAs in the abdominal adipose tissues were detected by Western blot and quantitative real time-PCR, separately. The CD68 expression (displaying infiltration of macrophages) of adipose tissue was detected using immunohistochemistry. RESULTS: After modeling, the contents of glucose of IPGTT at 30, 60 and 120 min and those of IPITT at 15, 30, 60 and 120 min, serum INS, CRP, IL-6 and TNF-α, as well as the expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein were significantly increased (P<0.01, P<0.05), while the levels of GIR and IL-10 protein and mRNA were obviously decreased in the model group in comparison with those of the control group (P<0.01), suggesting an increase of inflammation and a decline of INS sensitivity. Following the interventions, the increased contents of glucose of IPGTT and IPITT, serum INS, CRP, IL-6 and TNF-α, expression levels of IL-6, TNF-α, IL-1ß and MCP-1 proteins and mRNAs and CD68 protein, and the decreased levels of GIR and IL-10 protein and mRNA were evidently reversed in the EA group compared with the model group (P<0.01, P<0.05) rather than those in the sham EA group (P>0.05). CONCLUSION: EA can reduce the level of inflammation and improve insulin sensitivity in OIR rats.

[Network meta-analysis on the effects of the acupuncture-related therapy on ovulation rate and pregnancy rate in patients with polycystic ovary syndrome].

OBJECTIVE: To review systematically the safety and effectiveness of acupuncture-related therapies on ovulation rate and pregnancy rate in patients with polycystic ovary syndrome (PCOS). METHODS: From PubMed, EMbase, the Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database, the randomized controlled trials (RCTs) on PCOS were retrieved in the period from the date of database establishment to January 8, 2018. Two researchers screened the articles, extracted the data and assessed the bias risk of the eligible trials independently. Using Stata 13.0 and WinBUGS 1.4.3 software, the data were analyzed. RESULTS: A total of 39 RCTs were collected, including 4605 cases of PCOS and 14 kinds of acupuncture-related therapies and the comprehensive therapies. The short-term therapeutic effects were observed. The results of mesh meta-analysis showed: regarding the ovulation rate, the effects of the acupuncture-medication therapy were better than western medication. The top 6 therapeutic measures were the treatment with acupoint thread-embedding therapy and medication (93.3%), the treatment with moxibustion and Chinese herbal medicine (91.4%), moxibustion (74.5%), the treatment with acupuncture and medication (65.7%), the treatment with acupuncture-moxibustion and auricular point therapy (61.9%) and the treatment with acupuncture and auricular point therapy (49.6%). Regarding the pregnancy rate, the effects of the acupuncture-medication therapy were better than western medication. The top 6 therapeutic measures were the treatment with acupuncture and auricular point therapy (91.5%), the treatment with moxibustion and Chinese herbal medication (86.9%), the treatment with acupuncture-moxibustion and auricular point therapy (81.1%), the treatment with acupoint thread-embedding therapy and medication (69.4%), the treatment with acupuncture and medication (66.1%) and the treatment with placebo and western medication (58.7%). CONCLUSION: Among acupuncture-related therapies, the combined treatment is more advantageous than single therapy and its safety is superior to western medication. The combined therapies are various in advantages. Because of the limitation of the present researches, it needs a large scale of RCTs with rational design, high quality and proper methods to verify this research conclusion.